Archive for the ‘Skin Stem Cells’ Category

Reviewed by Sarah le Jeune, DVM, Dipl. ACVS, ECVS, ACVSMR, CVA, CVC

Classified among physical therapy/rehabilitation techniques, extracorporeal shock wave therapy (ESWT) remains an important tool for helping manage a variety of equine conditions/injuries.Issues amenable to ESWT in horses include, but are not limited to:

As you can see, this list primarily involves musculoskeletal conditions. Musculoskeletal injuries occur commonly in horses and all too frequently result in loss of use, early retirement, or even euthanasia. Combined with the fact that some injuries, such as lesions involving the superficial digital flexor tendon, have a propensity to recur despite extensive rest and controlled exercise programs,modalities such as ESWT continue to gain popularity in managing them.

Studies also support the use of ESWT in wound-healing. Many wounds affecting the lower parts of the equine limb heal slowly and often develop some degree of excessive scar (granulation) tissue, commonly referred to as proud flesh.

As with any intervention, seek your veterinarians advice prior to instituting therapy to avoid further compromising your horses well-being.

Described as both safe and effective, ESWT involves applying shock waves to an injured area of the body. Shock waves are intense but short energy pulses that travel so quicklya whopping 1,500 meters/ secondthey literally break the sound barrier. This is the same event that occurs when airplanes break the speed of sound, except in a much smaller format. The extracorporeal part of the name simply refers to the fact that the shock waves are generated outside the body.

A probe attached to a generator unit applies the shock waves directly to the injured region of the horse. Shock wave machines often have several probes capable of delivering shock waves to different tissue depths. This allows veterinarians to treat superficial injuries, such as wounds or lower limb tendons that are close to the skins surface, as well as deeper injuries, such as to muscles or back joints.

Veterinarians can adjust various settings on the shock wave unit to tailor the therapy to a horses individual needs. The three main settings vets must consider include:

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Shock Wave Uses and Benefits The Horse - TheHorse.com

During a Targeted Oncology case-based roundtable event, Nelson Jen An Chao, MD, discussed risk management and treatment of patients with steroid-refractory acute graft-versus-host-disease as well as chronic graft-versus-host disease.

Targeted OncologyTM: How do you stage and grade acute GVHD [aGVHD]?

CHAO: There are multiple ways of staging aGVHD. The Mount Sinai Acute GVHD International Consortium [MAGIC] has 2 staging systems, organ staging and overall clinical staging, which are based upon the most severe target organ involvement. The organ staging goes from 0 to 4 and its straightforward, focusing on the skin, liver, and upper GI [gastrointestinal] and lower GU [genitourinary]. It hasnt changed much; the main change in the last 10, maybe 15 years is the introduction of the upper GI GVHD, which includes nausea, vomiting, or anorexia. If you have those, youre at stage 1 and then the output is measured. It used to be just volume in the Glucksberg criteria in the past, but I think with the more current staging, the episodes are added into the GI staging as well.1

From the stage, the overall grade is developed, so grade 0 is none and then grade 1 is 2 skin symptoms without symptoms in any other organ. Grade 2 is skin symptoms with grade 1 symptoms of the liver or the gut, and so forth, and this gives one the ability to discuss GVHD staging and grading across trials.

[In 2012, investigators looked at a different system] to stratify the risk based on organ involvement and the number of organs involved. They looked at the grading of the organs of about 1600 patients and stratified based on standard vs high risk. For example, a single organ or just GI or liver with 2 organs was considered a standard risk. The high-risk group had very high single-organ magnification, like grade 4 skin, grade 3 to 4 GI, or grade 1 to 4 liver or 2 organs. If there are 3 organs, it is grade 1 to 3 of skin plus grade 3 to 4 of the gut or the liver. What they were able to do with this was by looking at this risk score, determine what the probability of response and probability to survival was.2

High-risk GVHD is associated with lower responses to steroids and higher treatment-related mortality. Standard-risk responders, both partial and complete responders, did much better than those at high risk. The probability of treatment-related mortality also is much higher for high-risk compared with standard-risk patients. This probably reflects the total amount of immunosuppression of these patients, as high-risk patients have a much more advanced-stage disease.

How do you approach treatment for a patient with steroid-refractory GVHD?

This patient has steroid-refractory resistance, which usually progresses within 3 to 5 days. If you dont get better within 5 to 7 days or after 20 days of immunosuppressive steroids, youre not improving as expected. Youre improving, but youre not much better. With steroid dependence, when you try to taper the patient, you get recurrence of aGVHD, and steroid intolerance is usually associated with unacceptable toxicity.3

The NCCN [National Comprehensive Cancer Network] has suggested agents for steroid-refractory GVHD. Ruxolitinib [Jakafi] is approved in the acute setting, but I think the key piece is clinical trials. We have lots of drugs, including alemtuzumab [Campath], and the approval for most of the drugs was based on studies with 30 patients in general that showed some response.In the chronic setting, ruxolitinib, belumosudil, and ibrutinib [Imbruvica] are approved.4

What is the evidence for using ruxolitinib in patients with steroid-refractory aGVHD?

Ruxolitinib is pretty good at inhibiting STAT signaling, which basically decreases the signaling of interferon and IL-17, both of which are proinflammatory cytokines. The phase 2 REACH-1 study [NCT02953678] enrolled 71 non-[randomly assigned] patients with aGVHD, who were treated with 5 mg ruxolitinib twice a day, and the primary end point was overall response at day 28.5,6

The overall response rate [ORR] at day 28 was 54.9%, with 26.8% achieving a complete response [(CR). On the whole,] the ORR was pretty good at 73% [CR, 56.3%]. The median time to response was 7 days [range, 6-49 days] and the duration of response [DOR], with more than 6 months of follow-up, was 345 days. There were [35] deaths [49.3%] and the nonrelapse mortality was fairly high at 44%, but the median OS [overall survival] for day 28 responders was not reached.7

These 71 patients went on to the phase 3 REACH2 study [NCT02913261]. This was a prospective randomized trial with 294 patients enrolled in a 1:1 randomization to ruxolitinib 10 mg twice a day or the best alternative therapy. Its an interesting design because the comparator included 10 different drugs [Figure7].

What were the results of REACH2?

[In the study,] you could use antithymocyte globulin, extracorporeal photopheresis [ECP], mesenchymal stromal cells, low-dose methotrexate, mycophenolate mofetil [MMF], everolimus [Afinitor] or sirolimus [Rapamune], etanercept [Enbrel], and infliximab [Remicade]. The numbers of patients enrolled in any one of these best alternative therapies was essentially driven by the institutions which enrolled these patients.6

The primary analysis was done on day 28 and these were patients who had severe refractory aGVHD grade 2 vs grade 3 and 4 and [who were aged] greater than 12 [years]. They had myeloid engraftment, butwere excluded if they had active infections or severe organ failure, if they had failed prior allogeneic hematopoietic stem cell transplant [HSCT] in the last 12 months, or if the disease had relapsed.

The study did allow for crossover, so if patients in the best alternative therapy group had not had a response by day 28 they could cross over to ruxolitinib. Then they looked at OS, event-free survival [EFS], and chronic GVHD [cGVHD].

The primary end point of the study was ORR at day 28, which was 63% for ruxolitinib compared with 39% in the control arm. Both partial responses [PRs] and CRs were higher with the ruxolitinib over the control arm, and durable responses were almost double for ruxolitinib [vs] the control on day 56 [odds ratio, 2.38; 95% CI, 1.43- 3.94; P < .001].8

When stratified by grade of disease, the odds ratios were significantly in favor of ruxolitinib. The odds ratio for the full analysis set was 2.64 [95% CI, 1.65-4.22]; for grade 2 it was [2.96 (95% CI, 1.30-6.76)], grade 3 was [2.15 (95% CI, 1.10-4.20)], and grade 4 was [3.76 (95% CI, 1.24-11.38)].8

The percentage of patients who lost response was much higher in the control groupover 40% compared with 10% to 15% in the ruxolitinib group. So patients taking ruxolitinib were much less likely to lose their response.8

Another interesting result was the shift in organ staging. Not every patient had a CR, but there was a shift to lower stages with ruxolitinib compared to the best alternative therapy. Overall, stage shifting downwards with ruxolitinib was better than [with] best alternative therapy.8

The failure-free survival [FFS] was quite significantly in favor of ruxolitinib. The percentage of patients without treatment failure was better with ruxolitinib [vs] the control. Obviously, this is not the answer to all of it and some patients are still failing therapy.8

Another cautionary point is that the toxicities are somewhat problematic with ruxolitinib. Thrombocytopenia is a known problem, and infections with CMV were perhaps a little higher than the control. But overall, the other adverse effects [AEs] were not very different between the 2 groups.8

Considering the REACH2 data, what do you use as first-line therapy for steroid-refractory aGVHD?

Ruxolitinib is an approved drug and I think its quite reasonable. I think many of us still have clinical trials ongoing or patients with steroid-refractory aGVHD, and if theres equipoise in the studies, the clinical trials could fall under the other section [of treatment decisions].

What are the therapeutic options for this patient?

The phase 3 REACH3 trial [NCT03112603] investigated the use of ruxolitinib in the chronic setting. The most remarkable part of this trial was the total number of patients: 329 patients enrolled with 1:1 randomization to 10 mg of ruxolitinib twice a day compared with best alternative therapy.

The best alternative therapies included ECP, low-dose methotrexate, MMF [mycophenolate mofetil], everolimus or sirolimus, infliximab, rituximab [Rituxan], pentostatin [Nipent], and imatinib [Gleevec]. The study did allow crossover to ruxolitinib after cycle 7, day 1, if the patient hadnt responded. The time for the initial response was 24 weeks, which looked at the overall response with CR plus PR, and the secondary end point was FFS and patients symptoms at week 24.9

What were the efficacy results of REACH3?

The response rates were higher for ruxolitinib, about 50% for ruxolitinib compared with 25% for the control on week 24. The best overall responses were 76% with both CRs and PRs compared with 60% with the best alternative therapy.9

The FFS was statistically significant for ruxolitinib, significantly better than the control arm, with the median FFS greater than 18.6 vs 5.7 months [HR, 0.37; 95% CI, 0.27-0.51; P < .001]. The DOR was also much better for ruxolitinib. The Kaplan-Meier median, estimating the probability of FFS at 6 months, was not reached for ruxolitinib compared with the control, which was 6.24 months.9

Are there other therapies to consider for this patient population?

In July of last year, the FDA approved belumosudil for [patients with] cGVHD after failure of at least 2 prior lines of systemic therapy. Thats the label indication, but the toxicity profile for the drug was significantly quite favorable and patients seemed to tolerate this very well. [These data are from] a randomized open-label trial with 65 patients.10

This [approval] was based on the ROCKstar study [NCT03640481], which was open label with 2 different doses at arm 1 with 200 mg a day and arm 2 with 200 mg twice a day. Theres no difference in the outcomes, so the recommended dose is once a day. The median time from cGVHD diagnosis was 25 months; 48% [of patients] had 4 more organs involved. The median number of prior lines of therapy was 3 and more than three-fourths [of patients] were refractory to the last therapy.11

There were clearly significant AEs for these drugs, but most would not make it difficult for the patients to tolerate this drug. Overall, it was quite well tolerated.

The ORR in the 200-mg arm was about 50% and the overall response occurring within the 12 months of therapy was quite high for these patients. FFS was 73% and the mean change was quite good, with about 50% of the patients improving. Overall, the clinically significant improvement from baseline was about 40% of these patients. So, good responses in a drug that was well tolerated.

REFERENCES

1. Harris AC, Young R, Devine S, et al. International, multicenter standardization of acute graft-versus-host disease clinical data collection: a report from the Mount Sinai Acute GVHD International Consortium. Biol Blood Marrow Transplant. 2016;22(1):4-10. doi:10.1016/j.bbmt.2015.09.001

2. MacMillan ML, Robin M, Harris AC, et al. A refined risk score for acute graft-versus-host disease that predicts response to initial therapy, survival, and transplant-related mortality. Biol Blood Marrow Transplant. 2015;21(4):761-767. doi:10.1016/j.bbmt.2015.01.001

3. Schoemans HM, Lee SJ, Ferrara JL, et al; EBMT (European Society for Blood and Marrow Transplantation) Transplant Complications Working Party and the EBMT-NIH (National Institutes of Health)-CIBMTR (Center for International Blood and Marrow Transplant Research) GvHD Task Force. EBMT-NIH-CIBMTR Task Force position statement on standardized terminology & guidance for graft-versus-host disease assessment. Bone Marrow Transplant. 2018;53(11):1401-1415. doi:10.1038/s41409-018-0204-7

4. NCCN. Clinical Practice Guidelines in Oncology. Hematopoietic cell transplantation (HCT), version 2.2021. Accessed April 23, 2021. https://bit.ly/3z4IyTn

5. Chao N. Finally, a successful randomized trial for GVHD. N Engl J Med. 2020;382(19):1853-1854. doi:10.1056/NEJMe2003331

6. Jagasia M, Zeiser R, Arbushites M, Delaite P, Gadbaw B, von Bubnoff N. Ruxolitinib for the treatment of patients with steroid-refractory GVHD: an introduction to the REACH trials. Immunotherapy. 2018;10(5):391-402. doi:10.2217/imt-2017-0156

7. Jagasia M, Perales MA, Schroeder MA, et al. Ruxolitinib for the treatment of steroid-refractory acute GVHD (REACH1): a multicenter, open-label phase 2 trial. Blood. 2020;135(20):1739-1749. doi:10.1182/blood.2020004823

8. Zeiser R, von Bubnoff N, Butler J, et al; REACH2 Trial Group. Ruxolitinib for glucocorticoid-refractory acute graft-versus-host disease. N Engl J Med. 2020;382(19):1800-1810. doi:10.1056/NEJMoa1917635

9. Zeiser R, Polverelli N, Ram R, et al; REACH3 Investigators. Ruxolitinib for glucocorticoid-refractory chronic graft-versus-host disease. N Engl J Med. 2021;385(3):228-238. doi:10.1056/NEJMoa2033122

10. FDA approves belumosudil for chronic graft-versus-host disease. Updated February 1, 2022. Accessed May 11, 2022. https://bit.ly/3NuPIEJ

11. Cutler C, Lee SJ, Arai S, et al. Belumosudil for chronic graft-versus-host disease after 2 or more prior lines of therapy: the ROCKstar study. Blood. 2021;138(22):2278-2289. Published correction appears in Blood. 2022;139(11):1772.

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Chao Discusses Stratifying and Treating Patients With Graft-Vs-Host Disease - Targeted Oncology

Sitting atop each kidney and measuring only around two centimeters long, the adrenal glands are tiny but mighty. These glands produce steroid hormones, including those involved in stress response, blood pressure maintenance, and fertility. When their development goes awry, it can cause a life-threatening condition called primary adrenal insufficiency, also known as Addisons disease. Many of the genetics involved in this and other adrenal gland disorders remain unknown.

Research on adrenal glands has often relied on insights made using mouse models. Now, a new study led by the School of Veterinary Medicines Kotaro Sasaki, which examined the developmental origin of the glands in humans and nonhuman primates, finds key developmental differences. This new understanding may inform diagnostics and treatment for Addisons disease and other endocrine system disorders.

The work was published in the journal Science Advances.

While some genetic causes of primary adrenal insufficiency have been identified, the mechanism has remained poorly understood, says Sasaki. Our findings help in identifying genes involved in adrenal development and could lead to new targets for therapeutic intervention.

Sasakis investigations have centered around studied gonadal development, how cells become ovaries or testes, organs that, like the adrenal gland, release hormones. Given this background, the adrenal gland was a natural next focus, especially because it has a shared origin with the gonads. In their recent work, Sasaki and colleagues looked at some of the earliest developmental stages to see how precursor cells and tissues evolve to give rise to the adrenal gland.

Scientists have long known that both the gonads and adrenal gland develop from a tissue known as the coelomic epithelium (CE), which is present at an early stage of embryonic development. In mice, for example, this tissue develops into the adrenogonadal primordium, which later divides to form both the adrenal primordium and the gonadal progenitor. The adrenal primodium goes on to become the adrenal gland, and the gonadal progenitor develops into either ovaries or testes.

Using immunofluorescence and in situ hybridization analyses, in which markers enable scientists to track cells descendants, Sasaki and his team found that primate CE expressed different genes than mouse CE. Whereas mice expressed the WT1, GATA4, and NR5A1 genes within the adrenogonadal primordium, primates did not express GATA4 in a parallel stage of development, a surprise to the researchers.

Whats more, while one portion of the primate CE led to the gonadal precursor, the other developed into the adrenal gland precursors, a division that wasnt present in mice.

It takes place in a way thats totally different from the mouse, says Sasaki. It appears that the portion of the coelomic epithelium that gives rise to the gonads is spatially separated from the part that gives rise to the adrenal gland.

Single-cell sequencing further revealed different patterns of gene expression between the adrenal and gonadal cell lineages, as well as a clear divergence between humans and mice. Some of these differentially expressed genes, Sasaki notes, are likely important in the process of deriving adrenal or gonadal tissues from CE.

Certain genes, Sasaki says, could also be examined in the context of adrenal insufficiency.

Currently, people with Addisons disease are treated with a lifelong steroid replacement therapy, using synthetic hormones to substitute for those that their bodies cant make on their own. Its not a cure and comes with serious side effects, Sasaki says.

In future work, he and colleagues hope to lay the groundwork in the lab to generate the adrenal cortex, employing inducible pluripotent stem cells, cells derived from blood or skin that can be induced to become a variety of different cell types. With such an approach, they could coax the stem cells to follow the normal developmental pathway toward becoming adrenal tissue. While in its early stages, this could enable a cell-based therapy for primary adrenal insufficiency, ideally avoiding some of the drawbacks of hormone replacement therapy.

Were pursuing in vitro studies to continue mapping out a blueprint that could be applicable to humans, Sasaki says.

Kotaro Sasaki is an assistant professor in the Department of Biomedical Sciences at the University of Pennsylvania School of Veterinary Medicine.

Sasakis coauthors were Penn Vets Keren Cheng, Yasunari Seita, Taku Moriwaki, Yuka Sakata, and Young Sun Hwang; Kiwamu Noshiro, Hidemichi Watari, and Takeshi Umazume of Hokkaido University; Toshihiko Torigoe of Sapporo Medical University; Mitinori Saitou of Kyoto University; Hideaki Tsuchiya and Chizuru Iwatani of Shiga University of Medical Science; Masayoshi Hosaka of the Fukuzumi Obstetrics and Gynecology Hospital; and Toshihiro Ohkouchi of Ohkouchi Obstetrics and Gynecology Hospital.

Sasaki was corresponding author and Cheng, Seita, and Moriwaki were co-first authors of the work, which was supported in part by the Japanese Science and Technology Agency (grants JPMJCE1301 and JPMJER1104), Silicon Valley Community Foundation, and Good Ventures Foundation.

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Elucidating the developmental origin of life-sustaining adrenal glands | Penn Today - Penn Today

It is a rather exciting month for beauty addicts because May has showered many launches upon us. From makeup to skincare, this month is packed with newbies some exciting, some innovative that make for productive additions to your vanity. With transitional weather (cloudy and heatwaves in equal parts), most of these products help you survive the maddening climate too. So, what are you waiting for? Scroll down and meet the latest beauty picks that deserve a spot in your shelfie.

iS Clinical Active Peel System

Meet the all-new two-step peel system from iS Clinical that treats the skin in just two steps, in fact just two pads. While the first pad is more like a target-based treatment while the second one is more hydrating. The duo comprises ingredients like copper tripeptides, AHAs and BHAs from fruits and an enzyme complex that exfoliates, hydrates and rejuvenates the skin, endowing multidimensional benefits. Some of which include boosted collagen production, minimised pores and wrinkles and improved skin texture.

PS: This is perfect to replace your nighttime skincare routine. Do not use any other product besides these two steps, when indulging in them.

Nykaa SkinRX Vitamin C Day Moisturizer

Before you think about the fact the brand had just launched moisturisers a while back, heres the catch these ones are oil-free. Super appropriate for the current hot and humid weather, this lightweight, gel-based cream is quick-absorbing and delivers decent moisture. This variant with vit C is best-suited for mornings, to keep sun damage at bay.

Anastasia Beverly Hills Magic Touch Concealer

Looking for a new concealer that blends out like a dream? This creamy formula does exactly that without caking up, thanks to the watery texture that (still) very effectively conceals dark spots and blemishes plus neutralising any unevenness.

Nashi Argan Sun Oil

Let me tell you Nashi Argan does one of the best argan oils out there that gives your hair a hug of *intense* nourishment. One of the most efficacious argan oil to smoothen locks, the best-selling oil has now been launched in a limited edition variant with UV protection infused in it, making it all the more better for this scorching season.

Revlon Colorstay Satin Ink

Revlon is out with yet another classic liquid lip that ties comfort and colour in one formulation, without even compromising minutely on either. With a high colour pay-off, this lippie wears comfortably and avoids all kinds of cracking and drying, courtesy of black currant seed oil. The best part? The creamy, shiny finish also has longevity. Plus, its available in some delicious colours.

Manish Malhotra Lip Liner & Filler

We all love (and need) a good lip liner, periodt. Now, before you worry about the tugging, let me introduce you to these just-in lip liners that make lip contouring a fun and comfortable experience. You can go ahead and fill-in your lips with em too, after all, they contain argan oil and hyaluronic acid to prevent chapped lips whatsoever.

Simply Nam Clean Lashes Mascara

Want to elevate your mascara application experience and the final look of it? Enter this mascara that has a whipped liquid formula that lengthens the lashes impressively without causing any clumps. In spite of this, its smudge-proof and waterproof, making it a holy grail for everyday wear in summers. Dont worry about flakiness it doesnt vandalise the lashes, thanks to avocado and jojoba oil. Extra points for the wand, thats as unique as it is effective.

Daughter Earth Under Eye Serum

Combining traditional gems with modern-age ingredients, the homegrown super brand has launched a much-needed product, yet again with triphala (amala, haritaki and bibhitaki) and apple stem cells (extract derived from the cells). Other noteworthy ingredients include caffeine, aloe, cucumber, watermelon and bakuchiol that help firm, tighten and brighten the under eye skin. Trust the lotion-textured serum to provide firmer, smoother and more youthful-looking eyes by alleviating signs of ageing and fatigue.

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All Things Hot In The Beauty Space In The Month Of May | Femina.in - Femina

Increasing Application of Stem Cells in Cosmetic Anti-aging Is Expected to Boost the Demand of Anti-aging Products and Therapies Market.

Anti-Aging Products and Therapies Market size is estimated to reach $93.2 billion by 2027, growing at a CAGR of 7.72% during the forecast period 2022-2027. Anti-Aging Products and Therapies are the products and therapeutics which defer, halt or hinder the aging process. Liposuction Surgery is an anti-aging therapy that is a fat elimination process that targets to destroy surplus stubborn fat from the hard-to-shift areas. Liposuction should be thought of as a sculpting process that can alter the curves of the body or face. A Tummy Tuck or Abdominoplasty is an anti-aging therapy that will eliminate surplus fat and skin from around the waist and eliminate surplus skin to leave a flatter, reduced body profile and younger-looking abdomen. Chemical peeling, also termed as chemexfoliation or derma-peeling, is an anti-aging therapy utilized to enhance the countenance of the skin in which a chemical solution is enforced on the skin, which brings about the blister and finally peels off. The novel, enhanced skin is normally smoother and less wrinkled than the old skin. The novel skin also is temporarily more sensitive to the sun. Anti-Pigmentation Therapy may include the application of anti-blemish and anti-pigmentation cream which is a blend of herbal concentrates that enhance the clearness of the skin.

The compelling technological developments in conjunction with emerging R&D activities have led to the launch of anti-aging treatments like liposuction, breast implants, and plastic surgeries are set to drive the Anti-Aging Products and Therapies Market. The increased awareness regarding aging amidst the youth and mature grown-ups is set to propel the growth of the Anti-Aging Products and Therapies Market during the forecast period 2022-2027. This represents the Anti-Aging Products and Therapies Industry Outlook.

Anti-Aging Products and Therapies Market Segment Analysis By Product:

The Anti-Aging Products and Therapies Market based on the product can be further segmented into Anti-Wrinkle Products, Anti-Stretch Mark Products, Hair Color Products, UV Absorption, and Others. The Anti-Wrinkle Products Segment held the largest market share in 2021. This growth is owing to the expanding population of the elderly requiring anti-wrinkle products. Typical anti-aging techniques include liposuction and chemical peeling. The heightened awareness regarding the accessibility of anti-wrinkle products is further propelling the growth of the Anti-Wrinkle Products segment.

Furthermore, the Anti-Stretch Mark Products segment is estimated to grow with the fastest CAGR of 8.41% during the forecast period 2022-2027 owing to the proliferating application of anti-stretch products in cases of stretch marks brought about by obesity and pregnancy in conjunction with more progressive products launched by key players for the treatment of stretch marks apart from the application of typical anti-aging techniques like chemical peeling.

Anti-Aging Products and Therapies Market Segment Analysis By Therapy:

The Anti-Aging Products and Therapies Market based on therapy can be further segmented into Liposuction, BOTOX, Rejuvenation & Dermal Fillers, Hormone Replacement Therapy, Gene Therapy, Sclerotherapy, Hair Restoration Services, Abdominoplasty, Anti-Pigmentation Therapy, Breast Augmentation, and Others. The Liposuction Segment held the largest market share in 2021. This growth is owing to the surging application of liposuction procedures largely attributed to their great recognition attained on social media. The goal of liposuction is esthetic. The proliferating technological progress and heightened awareness regarding liposuction procedures are further propelling the growth of this segment.

Furthermore, the BOTOX segment is estimated to grow with the fastest CAGR of 8.7% during the forecast period 2022-2027 owing to the surging application of botox injections largely ascribed to the health advantages offered like treatment of eye ailments like crossed eyes, smoothening wrinkles thereby minimizing signs of aging and offering alleviation for frequent migraine patients apart from the application of other anti-aging techniques like chemical peeling.

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Anti-Aging Products and Therapies Market Segment Analysis By Geography:

The Anti-Aging Products and Therapies Market based on geography can be further segmented into North America, Europe, Asia-Pacific, South America, and the Rest of the World. North America (Anti-Aging Products and Therapies Market) held the largest share with 36% of the overall market in 2021. The growth of this region is owing to the accessibility of well-developed infrastructure in the region. The soaring application of anti-aging therapies like liposuction and chemical peeling in the U.S. is further driving the growth of the Anti-Aging Products and Therapies Market in this region. The existence of key players like Merck in the U.S. in the region is further propelling the growth of the Anti-Aging Products and Therapies Market in the North American region.

Furthermore, the Asia-Pacific region is estimated to be the region with the fastest CAGR rate over the forecast period 2022-2027. This growth is owing to factors like soaring consumption of skincare products and cosmetics in emerging economies like India in the Asia-Pacific region. The detection of early signs of aging requiring the application of anti-aging techniques like chemical peeling is further fuelling the progress of the Anti-Aging Products and Therapies Market in the Asia-Pacific region

Anti-Aging Products and Therapies Market Drivers

Surging Advantages Of Chemical Peeling Are Projected To Drive The Growth Of Anti-Aging Products and Therapies Market:

Chemical peeling, also termed chemexfoliation or derma peeling, is a clinical process that utilizes plant-based chemical solutions to exfoliate the skin. Relying on the requirement of the client, a dermatologist may suggest a peel from a series of strengths: superficial peels that attain superficial layers of the skin or deeper ones that infiltrate numerous microlayers of skin. A chemical peeling treatment is a skin invigorating process, which utilizes gentle acids extracted from organic sources of changing strengths to exfoliate the upper layers of the skin in a regulated manner, succeeded by conversion of novel healthier layers. Chemical peeling assists in curbing acne breakouts by eliminating surplus sebum, dead skin cells, and dirt. It equalizes the texture of the skin by healthy skin invigoration. It enhances the complexion by minimizing dark spots and discoloration. The surging advantages of chemical peeling are therefore fuelling the growth of the Anti-Aging Products and Therapies Market during the forecast period 2022-2027.

Increasing Application Of Stem Cells In Cosmetic Anti-Aging Is Expected To Boost The Demand Of Anti-Aging Products and Therapies Market:

Typical anti-aging techniques include chemical peeling and liposuction. Stem cells are being utilized with heightening frequency in cosmetic medicine. Stem cells can be injected directly into the skin on the face and other areas. This has been demonstrated to minimize wrinkles, skin discoloration, and advance skin revitalization. It can also minimize the appearance of scars, stretch marks, and advance skin tightening. Investigations demonstrate that including stem cells in additional cosmetic surgeries like Liposuction, Fat Transfer Natural Breast Augmentation, and Awake Tummy Tuck, quicken healing and provide a superior cosmetic outcome. Adding stem cells to resurfacing lasers has been demonstrated to improve the ultimate outcomes as well. This is likely true when augmented with radiofrequency skin tightening as well. The increasing application of stem cells in cosmetic anti-aging is driving the growth of the Anti-Aging Products and Therapies Market during the forecast period 2022-2027.

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Anti-Aging Products and Therapies Market Challenges

Limitations Of Recognized Anti-Aging Treatments Are Hampering The Growth Of The Anti-Aging Products and Therapies Market:

Vitamin E is regarded as one of the most recognized skin anti-aging agents, both as an oral and topical treatment. However, Vitamin E is not regarded safe at the time of pregnancy. Consuming vegetables will not hurt the baby. However, it is presently unclear at what levels Vitamin E supplements become hazardous to unborn babies. Nearly all physicians suggest not to consume more than 400 IU/day. To be entirely efficient as an anti-aging product, vitamin E needs to be consumed orally creams with vitamin E can smoothen and contribute elasticity. However, the actual advantages come from pills and not everyone likes to take pills. Another technique is Botox. Botox is good but not all-inclusive. It is not efficient at combating those wrinkles around the mouth or wrinkles brought about by sun damage. In addition, it will not perform for everyone in an identical manner. These issues are hampering the growth of the Anti-Aging Products and Therapies Market.

Anti-Aging Products and Therapies Market Landscape:

Product launches, mergers and acquisitions, joint ventures, and geographical expansions are key strategies adopted by players in the Anti-Aging Products and Therapies Market. Key companies of this market are:

GaoxinMerckIMEIKBohus BioTechLG Life ScienceGaldermalAllerganIpsenLanzhou InstituteCynosure

Recent Developments

In January 2022, Chanel has introduced a series of skincare and cosmetic products described by Vogue as its most environmentally conscious to date, inclusive of its earliest refillable beauty product. The series of products, termed No. 1 de Chanel, is housed in packaging with no exterior plastic wrapping and no interior paper leaflets. Chanel has also discarded all plastic constituents in the bottles and jars, choosing glass instead and persuading customers to recycle the packaging once it is vacant.

In October 2021, Cynosure declared the Canadian (Health Canada) clearance of its best-in-class Potenza radiofrequency (RF) microneedling system providing clinicians incomparable versatility and customized treatments for patients with its one-of-a-kind Fusion Tip. The novel standard in RF microneedling, the Potenza devices four modes (monopolar or bipolar, conveyed at either 1 MHz or 2 MHz frequency), provides more personalized microneedling treatments for patients than ever before, which permits practitioners to convey both shallow and deep treatments on a single system. The devices monopolar RF mode conveys energy across a big area of tissue for deep heating and skin tightening by way of soft tissue coagulation, not only on the face but also anywhere on the body.

In October 2020, Cynosure declared the U.S. and Canadian introduction of FlexSureTM, the most-recent inclusion to its best-in-class TempSure 300-watt platform and the worlds earliest wrappable radiofrequency (RF) applicator for malleable, hands-free, non-invasive RF treatments. With its rare peel-and-stick single-application applicators, the body-boosting FlexSure treatment conveys deep tissue heating to numerous body parts, inclusive of the abdomen, flanks, back, arms, buttocks, thighs, and above the knees. Accessible in numerous sizes, each equipped with six customizable zones and real-time temperature-sensing capacities, the FlexSure device permits practitioners to carry out constant, quick, and efficient treatments in just 15 minutes per body area.

Key Takeaways

Geographically, North America Anti-Aging Products and Therapies Market accounted for the highest revenue share in 2021 and it is poised to dominate the market over the period 2022-2027 owing to the soaring awareness of aging signs resulting in the application of anti-aging therapies like liposuction and increasing obesity in the North American region.

Anti-Aging Products and Therapies Market growth is being driven by the expanding population of the elderly, surging demand for cosmetic products, and the emerging beauty consciousness amidst youth worldwide resulting in the application of anti-aging therapies like liposuction. However, the binding rules and regulations imposed by the government in endorsing novel products and the fluctuations in the accessibility of raw materials are directly impacting the ultimate price of products which is one of the major factors hampering the growth of the Anti-Aging Products and Therapies Market.

Anti-Aging Products and Therapies Market Detailed Analysis on the Strength, Weakness and Opportunities of the prominent players operating in the market will be provided in the Anti-Aging Products and Therapies Market report.

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Anti Aging Market

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Anti-Aging Products and Therapies Market Size Estimated to Reach $93.2 Billion by 2027 - Digital Journal

image:zebrafish notochord nuclei at 15-somite stage. Grey: nuclear DNA (DAPI). Color: histone H3K9me3 view more

Credit: Phong Nguyen, Franka Rang & Kim de Luca. Copryight Hubrecht Institute.

How is the activity of genes regulated by the packaging of DNA? To answer this question, a technique to measure both gene expression and DNA packaging at the same time was developed by Franka Rang and Kim de Luca, researchers from the group of Jop Kind (group leader at the Hubrecht Institute and Oncode Investigator). This method, EpiDamID, determines the location of modified proteins around which the DNA is wrapped. It is important to gather information about these modifications, because they influence the accessibility of DNA, thereby affecting the gene activity. EpiDamID is therefore valuable for research into the early development of organisms. The results of the study are published in Molecular Cell on April 1st 2022.

In order to fit DNA into the nucleus of a cell, it is tightly packed around nuclear proteins: histones. Depending on the tightness of this winding, the DNA can be (in)accessible to other proteins. This therefore determines whether the process of gene expression, translation of DNA into RNA and eventually into proteins, can take place.

DNA packaging determine gene activity

The tightness of DNA winding around histones is regulated by the addition of molecular groups, so-called post-translational modifications (PTMs), to the histones. For example, if certain molecules are added to the histones, the DNA winding is loosened. This makes the DNA more accessible for certain proteins and causes the genes in this part of the DNA to become active, or expressed. Furthermore, proteins that are crucial for gene expression can directly recognize and bind the PTMs. This enables transcription: the process of DNA copying.

The regulation of gene expression, for instance through PTMs, is also known as epigenetic regulation. Since all cells in a body have the same DNA, regulation of gene expression is needed to (de)activate specific functions in individual cells. For instance, heart muscle cells have different functions than skin cells, thus require different genes to be expressed.

Analysis of single cells using EpiDamID

To understand how PTMs affect gene expression, first authors Franka Rang and Kim de Luca designed a new method to determine the location of the modifications. Using this approach, called EpiDamID, researchers can analyze single cells, whereas previous methods were only able to measure a large group of cells. Analysis on such a small scale results in knowledge on how DNA winding differs per cell, rather than information on the average DNA winding of many cells.

EpiDamID is based on DamID, a technique which is used to determine the binding location of certain DNA-binding proteins. Using EpiDamID, the binding location of specific PTMs on histone proteins can be detected in single cells. Compared to others, a great advantage of this technique is that researchers need very limited material. Furthermore, EpiDamID can be used in combination with other methods, such as microscopy, to study regulation of gene expression on different levels.

Future prospects

Following the development of this technique, the Kind group will focus on the role of PTMs from the point of view of developmental biology. Because single cells are analyzed using EpiDamID, only a limited amount of material is needed to generate enough data. This allows researchers to study the early development of organisms from its first cell divisions, when the embryo consists of only a few cells.

###

Publication

Rang, F. J.*, de Luca, K. L.*, de Vries, S. S., Valdes-Quezada, C., Boele, E., Nguyen, P. D., Guerreiro, I., Sato, Y., Kimura, H., Bakkers, J. & Kind, J. Single-cell profiling of transcriptome and histone modifications with EpiDamID. Molecular Cell, 2022.

*Authors contributed equally

Jop Kind is group leader at the Hubrecht Institute for Developmental Biology and Stem Cell Research and Oncode Investigator.

About the Hubrecht Institute

The Hubrecht Institute is a research institute focused on developmental and stem cell biology. It encompasses 21 research groups that perform fundamental and multidisciplinary research, both in healthy systems and disease models. The Hubrecht Institute is a research institute of the Royal Netherlands Academy of Arts and Sciences (KNAW), situated on Utrecht Science Park. Since 2008, the institute is affiliated with the UMC Utrecht, advancing the translation of research to the clinic. The Hubrecht Institute has a partnership with the European Molecular Biology Laboratory (EMBL). For more information, visit http://www.hubrecht.eu.

Experimental study

Cells

Single-cell profiling of transcriptome and histone modifications with EpiDamID

1-Apr-2022

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

Original post:
Learning from the single cell: A new technique to unravel gene regulation - EurekAlert

Cell and gene therapies are poised to have a major impact on the landscape of modern medicine, carrying the potential to treat an array of different diseases with unmet clinical need.

However, the number of approved, clinically adopted cell and gene therapies is mere compared to the amount that are currently in development. A major barrier for the translation of such therapies is the safe integration of therapeutic genes into the human genome. The insertion of therapeutic genes bears the risk of off target effects, or integration of the gene into an unintended location.

A number of different strategies have been proposed to mitigate this effect. The most recent body of work comes from a collaboration between Harvards Wyss Institute for Biologically Inspired Engineering, Harvard Medical School (HMS) and the ETH Zurich in Switzerland.

Published in Cell Report Methods, the research focused on identifying safe spots in the genome. These locations, known as genomic safe harbors (GSHs), are areas in the genome that meet the following criteria: they can be accessed easily by genome-editing strategies, are within a safe distance from genes that possess functional properties and permit expression of a therapeutic gene, only once it has landed in the harbor. A simple analogy is deciding which harbor to dock a boat there are many considerations, and these depend on the type of boat you are sailing, the weather conditions and ease of access.

The research team adopted computational strategies that enabled the identification of 2,000 predicted GSHs. From this initial identification, they successfully validated two of the sites both in vitro and in vivo using reporter proteins.

Technology Networks interviewed the studys first author, Dr. Erik Aznauryan, research fellow in the laboratory of Professor George Church at Harvard Medical School. Aznauryan dives into further detail on the history of GSH research, the methods adopted to validate the GSH sites and the potential applications of this research.

Molly Campbell (MC): Can you talk about the history of genomic safe harbor research, and how they were discovered?

Erik Aznauryan (EA): Three genomic sites were empirically identified in previous studies to support stable expression of genes of interest in human cells: AAVS1, CCR5 and hRosa26. All these examples were established without any a-priori safety assessment of the genomic loci they reside in.

Attempts have been made to identify human GSH sites that would satisfy various safety criteria, thus avoiding the disadvantages of existing sites. One approach developed by Sadelain and colleagues used lentiviral transduction of beta-globin and green fluorescence protein genes into induced pluripotent stem cells (iPSCs), followed by the assessment of the integration sites in terms of their linear distance from various coding and regulatory elements in the genome, such as cancer genes, miRNAs and ultraconserved regions.

They discovered one lentiviral integration site that satisfied all of the proposed criteria, demonstrating sustainable expression upon erythroid differentiation of iPSCs. However, global transcriptome profile alterations of cells with transgenes integrated into this site were not assessed. A similar approach by Weiss and colleagues used lentiviral integrations in Chinese hamster ovary (CHO) cells to identify sites supporting long-term protein expression for biotechnological applications (e.g., recombinant monoclonal antibody production). Although this study led to the evaluation of multiple sites for durable, high-level transgene expression in CHO cells, no extrapolation to human genomic sites was carried out.

Another study aimed at identifying GSHs through bioinformatic search of mCreI sites regions targeted by monomerized version of I-CreI homing endonuclease found and characterized in green algae as capable to make targeted staggered double-strand DNA breaks residing in loci that satisfy GSH criteria. Like previous work, several stably expressing sites were identified and proposed for synthetic biology applications in humans. However, local and global gene expression profiling following integration events in these sites have not been conducted.

All these potential GSH sites possess a shared limitation of being narrowed by lentiviral- or mCreI-based integration mechanisms. Additionally, safety assessments of some of these identified sites, as well as previously established AAVS1, CCR5 and Rosa26, were carried out by evaluating the differential gene expression of genes located solely in the vicinity of these integration sites, without observing global transcriptomic changes following integration.

A more comprehensive bioinformatic-guided and genome-wide search of GSH sites based on established criteria, followed by experimental assessment of transgene expression durability in various cell types and safety assessment using global transcriptome profiling would, thus, lead to the identification of a more reliable and clinically useful genomic region.

MC: If GSHs do not encode proteins, or RNAs with functions in gene expression, or other cellular processes what is their function in the genome?

EA: In addition to protein coding, functional RNA coding, regulatory and structural regions of the human genome, other less well understood and inactive DNA regions exist.

A large proportion of the human genome seems to have evolved in the presence of a variety of integrating viruses which, as they inserted their DNA into the eukaryotic genome over the course of million years, lead to an establishment of vast non-coding elements that we continue to carry to this day. Furthermore, partial duplications of functional human genes have resulted in the formation of inactive pseudogenes, which occupy space in the genome yet are not known to bear cellular functions.

Finally, functional roles of some non-coding portions of the human genome are not well understood yet. Our search of safe harbors was conducted using existing annotation of the human genome, and as more components of it are deciphered the identification of genomic regions safe for gene insertion will become more informed.

MC: Are you able to discuss why some regions of the genome were previously regarded as GSHs but are now recognized as non-GSHs?

EA: In the absence of other alternatives, AAVS1, CCR5 and hRosa26 sites were historically called GSHs, as they supported the expression of genes of interest in a variety of cell types and were suitable for use in a research setting.

Their caveats (mainly, location within introns of functional genes, closely surrounded by other known protein coding genes as well as oncogenes) however prevent them from being used for clinical applications. Therefore, in our paper we dont call them GSHs, and refer to our newly discovered sites as GSHs.

MC: You thoroughly scanned the genome to identify candidate loci for further study as potential GSHs. Can you discuss some of the technological methods you adopted here, and why?

EA: We used several publicly available databases to identify genomic coordinates of structural, regulatory and coding components of the human genome according to the GSH criteria we outlined in the beginning of our study (outside genes, oncogenes, lncRNAs etc.,). We used these coordinates and bioinformatic tools such as command lines bedtools to exclude these genomic elements as well as areas adjacent to them. This left us with genomic regions putative GSHs from which we could then experimentally validate by inserting reporter and therapeutic genes into them followed by transcriptomic analysis of GSH-integrated vs non-integrated cells.

MC: You narrowed down your search to test five, and then two GSHs. Can you expand on your choice of reporter gene when assessing two GSHs in cell lines?

EA: Oftentimes in research you go with what is available or what is of the most interest to the lab you are currently working in.

Our case was not an exception, and we initially (up until the T cell work) used the mRuby reporter gene as it was widely available and extensively utilized and validated in our lab at ETH Zurich back then.

When I moved to the Wyss Institute at Harvard, I began collaborating with Dr. Denitsa Milanova, who was interested in testing these sites in the context of skin gene therapy particularly the treatment of junctional epidermolysis bullosa caused by mutations in various anchor proteins connecting different layers of skin, among which is the LAMB3 gene. For this reason, we decided to express this gene in human dermal fibroblasts, together with green fluorescent protein to have a visualizable confirmation of expression. We hope we would be able to translate this study into clinics.

MC: Can you describe examples of how GSHs can be utilized in potential therapeutics?

EA: Current cell therapy approaches rely on random insertion of genes of interest into the human genome. This can be associated with potential side effects including cancerous transformation of therapeutic cells as well as eventual silencing of the inserted gene.

We hope that current cell therapies will eventually transition to therapeutic gene insertions precisely into our GSHs, which will alleviate both described concerns. Specific areas of implementation may involve safer engineering of T cells for cancer treatment: insertion of genes encoding receptors targeting tumor cells or cytokines capable of enhancing anti-tumor response.

Additionally, these sites can be used for the engineering of skin cells for therapeutic (as discussed earlier with the LAMB3 example) as well as anti-aging applications, such as expression of genes that result in youthful skin phenotype.

Finally, given the robustness of gene expression from our identified sites, they can be used for industry-scale bio-manufacturing: high-yield production of proteins of interest in human cell lines for subsequent extraction and therapeutic applications (e.g., production of clotting factors for patients with hemophilias).

MC: Are there any limitations to the research at this stage?

EA: A primary limitation to this study is the low frequency of genomic integration events using CRISPR-based knock-in tools. This means that cells in which the gene of interest successfully integrated into the GSH must be pulled out of the vastly larger population of cells without this integration.

These isolated cells would then be expanded to generate homogenous population of gene-bearing cells. Such pipeline is not ideal for a clinical setting and improvements in gene integration efficiencies are needed to help this technology easier translate into clinics.

Our lab is currently working on developing genome engineering tools which would eventually allow to integrate large genes into GSHs with high precision and efficiency.

MC: What impact might this study have on the cell and gene therapy development space?

EA: This study will hopefully lead to many researchers in the field testing our sites, validating them in other therapeutically relevant cell types and eventually using them in research as well as in clinics as more reliable, durable and safe alternatives to current viral based random gene insertion methods.

Additionally, since in our work we shared all putative GSHs identified by our computational pipeline, we hope researchers will attempt to test sites we havent validated yet by implementing the GSH evaluation pipeline that we outlined in the paper. This will lead to identification of more GSHs with perhaps even better properties for clinical translation or bio-manufacturing.

MC: What are your next steps in advancing this work?

We hope to one day translate our successful in vitro skin results and start using these GSHs in an in vivo context.

Additionally, we are looking forward to improving integration efficiencies into our GSHs, which would further support clinical transition of our sites.

Finally, we will evaluate the usability of our GSHs for large-scale production of therapeutically relevant proteins, thus ameliorating the pipeline of manufacturing of biologics.

Dr. Erik Aznauryan was speaking to Molly Campbell, Senior Science Writer for Technology Networks.

View original post here:
Sailing the Genome in Search of Safe Harbors - Technology Networks

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The following discussion of our financial condition and results of operationsshould be read in conjunction with our audited consolidated financial statementsand related notes and other financial information included elsewhere in thisAnnual Report on Form 10-K. The discussion contains forward-looking statements,such as our plans, expectations and intentions (including those related toclinical trials and business and expense trends), that are based upon currentexpectations and that involve risks and uncertainties. Our actual results maydiffer significantly from management's expectations. The factors that couldaffect these forward-looking statements are in Item 1A of Part I of this report.This discussion should not be construed to imply that the results discussedherein will necessarily continue into the future, or that any expectationsexpressed herein will necessarily be indicative of actual operating results inthe future. Such discussion represents only the best present assessment by ourmanagement.

Business Overview

We have generated aggregate product revenues from our two commercial businessesof $7.2 million and $7.1 million for the years ended December 31, 2021 and 2020,respectively. We currently have no revenue generated from our principaloperations in therapeutic and clinical product development.

Our products are based on multi-decade experience with human cell culture and aproprietary type of pluripotent stem cells, human parthenogenetic stem cells("hpSCs"). Our hpSCs are comparable to human embryonic stem cells ("hESCs") inthat they have the potential to be differentiated into many different cells inthe human body. However, the derivation of hpSCs does not require the use offertilized eggs or the destruction of viable human embryos and also offers thepotential for the creation of immune-matched cells and tissues that are lesslikely to be rejected following transplantation. Our collection of hpSCs, knownas UniStemCell, currently consists of 15 stem cell lines. We have facilitiesand manufacturing protocols that comply with the requirements of GoodManufacturing Practice (GMP) standards as promulgated by the U.S. Code ofFederal Regulations and enforced by the United States Food and DrugAdministration ("FDA").

COVID-19 Pandemic

The impact of the COVID-19 pandemic has been and will likely continue to beextensive in many aspects of society, which has resulted in and will likelycontinue to result in significant disruptions to the global economy, as well asbusinesses and capital markets around the world. Impacts to our business haveincluded a reduction in sales volume primarily from media sales in ourbiomedical market segment and professional channel sales in our anti-agingmarket segment, temporary or reduced occupancy of portions of our manufacturingfacilities, and disruptions or restrictions on our employee's ability to travelto such manufacturing facilities which caused minor delays in manufacturing. Ourmanufacturing facilities continue to operate as they are deemed essentialsuppliers in accordance with laws applicable to California and Maryland. We havetaken precautionary measures to better ensure the health and safety of ourworkers, including staggering employees' shifts and isolating at-risk employees.

The scope and duration of these delays and disruptions, and the ultimate impactsof COVID-19 on our operations, are currently unknown. We are continuing toactively monitor the situation and may take further precautionary and preemptiveactions as may be required by federal, state or local authorities or that wedetermine are in the best interests of public health and safety. We cannotpredict the effects that such actions, or the impact of COVID-19 on globalbusiness operations and economic conditions, may continue to have on ourbusiness, strategy, collaborations, or financial and operating results.

Market Opportunity and Growth Strategy

Therapeutic Market - Clinical Applications of hpSCs for Disease Treatments

With respect to therapeutic research and product candidates, we focus onapplications where cell and tissue therapy is already proven but where there isan insufficient supply of safe and functional cells or tissue. We believe thatthe most promising potential clinical applications of our technology are: 1)Parkinson's disease ("PD"); and 2) traumatic brain injury ("TBI"). Using ourproprietary technologies and know-how, we are creating neural stem cells fromhpSCs as a potential treatment of PD, TBI and stroke.

Our most advanced project is the neural stem cell program for the treatment ofParkinson's disease. In 2013 we published in Nature Scientific Reports the basisfor our patent on a new method of manufacturing neural stem cells which is usedto produce the clinical-grade cells necessary for future clinical studies andcommercialization. In 2014 we completed the majority of the preclinical researchestablishing the safety profile of NSC in various animal species includingnon-human primates. In June 2016 we published the results of a 12-monthpre-clinical non-human primate study, which demonstrated the safety, efficacyand mechanism of action of the ISC- hpNSC. In 2017 we dosed four patients inour Phase I trial of ISC-hpNSC, human parthenogenetic stem cell-derived neuralstem

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cells for the treatment of Parkinson's disease. We reported 12-month resultsfrom the first cohort and 6-month interim results of the second cohort at theSociety for Neuroscience annual meeting (Neuroscience 2018) in November 2018. InApril 2019, we announced the completion of subject enrollment, with the 12thsubject receiving a transplantation of the highest dose of cells. There havebeen no safety signals or serious adverse effects seen to date as related to thetransplanted ISC-hpNSC cells.

In August 2014 we announced the launch of a stroke program, evaluating the useof ISC-hpNSC transplantation for the treatment of ischemic stroke using arodent model of the disease. The Company has a considerable amount of safetydata on ISC-hpNSC from the Parkinson's disease program and, as there isevidence that transplantation of ISC-hpNSC may improve patient outcomes as anadjunctive therapeutic strategy in stroke, having a second program that can usethis safety dataset is therefore a logical extension. In 2015 the Companytogether with Tulane University demonstrated that NSC can significantly reduceneurological dysfunction after a stroke in animal models.

In October 2016 we announced the results of the pre-clinical rodent study,evaluating the use of ISC-hpNSC transplantation for the treatment of TBI. Thestudy was conducted at the University of South Florida Morsani College ofMedicine. We demonstrated that animals receiving injections of ISC-hpNSCdisplayed the highest levels of improvements in cognitive performance and motorcoordination compared to vehicle control treated animals. In February 2019, wepublished the results of the pre-clinical study in Theranostics, a prestigiouspeer-reviewed medical journal. The publication titled, "Human parthenogeneticneural stem cell grafts promote multiple regenerative processes in a traumaticbrain injury model," demonstrated that the clinical-grade neural stem cells usedin our Parkinson's disease clinical trial, ISC-hpNSC, significantly improvedTBI-associated motor, neurological, and cognitive deficits without any safetyissues.

Anti-Aging Cosmetic Market - Skin Care Products

Our wholly-owned subsidiary LSC develops, manufactures and offers for saleanti-aging skin care products based on two core technologies: encapsulatedextract derived from hpSC and specially selected targeted small molecules. LSC'sproducts include:

LSC's products are regulated as cosmetics. LSC's products are sold domesticallythrough a branded website, Amazon, ecommerce partners and through theprofessional channel (including dermatologists, plastic surgeons, medical, dayand resort spas).

Biomedical Market - Primary Human Cell Research Products

Our wholly-owned subsidiary LCT develops, manufactures and commercializesapproximately 200 human cell culture products, including frozen human "primary"cells and the reagents (called "media") needed to grow, maintain anddifferentiate the cells. LCT's scientists have used a standardized, methodical,scientific approach to basal medium optimization to systematically produceoptimized products designed to culture specific human cell types and to elicitspecific cellular behaviors. These techniques can also be used to produceproducts that do not contain non-human animal proteins, a feature desirable tothe research and therapeutic markets. Each LCT cell product is quality testedfor the expression of specific markers (to assure the cells are the correcttype), proliferation rate, viability, morphology and absence of pathogens. Eachcell system also contains associated donor information and all informed consentrequirements are strictly followed. LCT's research products are marketed andsold by its internal sales force, OEM partners and LCT brand distributors inEurope and Asia.

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Results of Operations

Comparison of the Years Ended December 31, 2021 and 2020

Product sales revenue for the year ended December 31, 2021 was $7.2 million,compared to $7.1 million for the year ended December 31, 2020. The increase wasprimarily attributable to a $342 thousand increase in sales in our biomedicalmarket segment, largely offset by a $294 thousand decrease in sales in ouranti-aging market during 2021 compared to 2020.

Our biomedical product sales continue to recover from the impacts of COVID-19 aspurchasing activity from our largest original equipment manufacturer customersincreases.

Our professional skin care products, which are largely marketed to medicalprofessionals and spas that offer walk-up retail, experienced a significantdecline in customer demand due to COVID-19 and the related restrictions as thesebusinesses have continued with limited or reduced operations during the yearended December 31, 2021. The impact of these restrictions was mitigated in-partby expanding our offering of professional skin care products through ourecommerce channel. Anti-aging product sales through our ecommerce channelremained consistent year-over-year.

Cost of Sales

Cost of sales for the year ended December 31, 2021 was $2.9 million, compared to$2.8 million for the year ended December 31, 2020. The increase was primarilyattributable to an increase in costs as a result of an increase in productsales. Profit margins have deteriorated for the year ended December 31, 2021 ascompared to 2020, largely as a result of rising raw materials and labor relatedcosts, and a scarcity of certain materials, principally plastics. In response,we have increased our supply of raw materials on hand and have, where possible,sourced materials from alternative vendors.

Cost of sales consists primarily of salaries and benefits associated withemployee efforts expended directly on the production of the Company's products,as well as related direct materials, general laboratory supplies and anallocation of overhead. We aim to continue refining our manufacturing processesand supply chain management to improve the cost of sales as a percentage ofrevenue for both LCT and LSC.

General and Administrative Expenses

General and administrative expenses for the year ended December 31, 2021 was$4.1 million, compared to $4.4 million for the year ended December 31, 2020. Thedecrease was primarily attributable to a decrease in personnel-related costs andstock-based compensation of $522 thousand, a $87 thousand decrease in consultingand servicing fees, and a $26 thousand decrease in investor relations fees,partially offset by an increase in impairment of intangible assets of$184 thousand, a $57 thousand increase in director and officer liabilityinsurance premiums, a $24 thousand increase in human resource related expenses,a $16 thousand gain on foreign currency exchange rate conversion, and a$15 thousand increase in filing fees.

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Selling and Marketing Expenses

Selling and marketing expenses for the year ended December 31, 2021 was$1.4 million, compared to $1.8 million for the year ended December 31, 2020. Thedecrease was primarily attributable to a $178 thousand decrease inpersonnel-related costs, sales commissions and stock-based compensation,primarily as a result of headcount reductions and grants from 2018 which wereissued and fully vested in 2021, and a $211 thousand decrease in marketing,advertising, and building related expenses, partially offset by a $17 thousandincrease in consulting and creative service fees. The reduction in marketing,advertising, and building related expenses was largely attributable to travelrestrictions as a result of COVID-19.

Research and Development Expenses

Research and development expenses for the year ended December 31, 2021 was$0.7 million, compared to $1.0 million for the year ended December 31, 2020. Thedecrease was primarily attributable to a $247 thousand decrease inpersonnel-related costs and stock-based compensation primarily as a result ofheadcount reductions and grants from 2018 which were issued and fully vested in2021, a $89 thousand decrease in materials and supplies related to clinicaltrial expenses, a $46 thousand decrease in consulting services, partially offsetby a $45 thousand increase in building and utilities related expenses and a$44 thousand decrease in our research and development tax credit related toqualifiable expenditures from our research and development activities of ourAustralia subsidiary, Cyto Therapeutics, which reduced research and developmentexpenses for years ended December 31, 2021 and 2020.

Our research and development efforts are primarily focused on the development oftreatments for Parkinson's disease, traumatic brain injury, liver diseases,stroke, and the creation of new GMP grade human parthenogenetic stem cell lines.These projects are long-term investments that involve developing both new stemcell lines and new differentiation techniques that can provide higher puritypopulations of functional cells. Research and development expenses are expensedas incurred and are accounted for on a project-by-project basis. However, muchof our research has potential applicability to each of our projects. As wecompleted Phase 1 of our clinical in June 2021, we do not anticipate significantinvestment in research and development efforts related to therapeutic andclinical product development efforts for the foreseeable future, or until suchtime that we initiate a Phase 2 clinical trial.

Other Income, Net

Other income, net, for the year ended December 31, 2021 was $1.0 million,compared to other income, net, of $94 thousand for the year endedDecember 31, 2020. The increase was primarily attributable to forgiveness of ourFirst Draw Loan and Second Draw Loan from the PPP, collectively totaling$1.1 million, partially offset by a decrease of $207 thousand for the change inthe fair value of the warrant liability during the prior year period. Thewarrants expired unexercised in March 2021 and, as such, no further change inthe fair value of the warrant liability will be recognized.

Liquidity and Capital Resources

As of December 31, 2021, we had an accumulated deficit of approximately$110 million and have, on an annual basis, incurred net losses and negativeoperating cash flows since inception. Substantially all of our operating losseshave resulted from the funding of our research and development programs andgeneral and administrative expenses associated with our operations. We incurrednet losses of $0.9 million and $2.7 million for years ended December 31, 2021and 2020, respectively. As of December 31, 2021, we had cash of $171 thousand,compared to $689 thousand as of December 31, 2020.

In May 2020, we received a first draw loan of $654 thousand from the PPP ("FirstDraw Loan") which provided additional liquidity to support our currentoperations. In March 2021, we received a second draw loan of $474 thousand fromthe PPP ("Second Draw Loan"). In June 2021, we applied for and receivedforgiveness of unpaid principal and accrued interest from our First Draw Loan inthe amount of $661 thousand. In August 2021, we applied for and receivedforgiveness of unpaid principal and accrued interest from our Second Draw Loanin the amount of $476 thousand. As of December 31, 2021, we are not eligible toreceive any additional funding, or have any further obligations, related to thePPP.

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Cash Flows

Comparison of the Years Ended December 31, 2021 and 2020

The following table provides information regarding our cash flows for the yearsended December 31, 2021 and 2020 (in thousands):

Net cash used in operating activities $ (1,297 ) $ (341 )Net cash used in investing activities

Operating Cash Flows

For the year ended December 31, 2021, net cash used in operating activities was$1.3 million, resulting primarily from our net loss of $899 thousand and netchanges in operating assets and liabilities of $823 thousand, consistingprimarily of an increase in accounts receivable of $441 thousand, inventory,net, of $268 thousand, and decrease in operating lease liabilities of $342thousand, partially offset by net non-cash adjustments of $425 thousand. For theyear ended December 31, 2020, net cash used in operating activities was$341 thousand, resulting primarily from our net loss of $2.7 million and changein fair value of warrant liability of $207 thousand, offset by non-cashadjustments of stock-based compensation expense of $1.3 million, operating leaseexpense of $265 thousand and depreciation and amortization of $253 thousand,coupled with net changes in operating assets and liabilities of $623 thousand.

Investing Cash Flows

Net cash used in investing activities for the year ended December 31, 2021 was$45 thousand, compared to $108 thousand for the year ended December 31, 2020.The decrease was attributable to a decrease in payments for patent licenses of$58 thousand and purchases of property and equipment of $5 thousandyear-over-year.

Financing Cash Flows

Net cash provided by financing activities for year ended December 31, 2021 was$0.8 million, compared to $0.7 million for the year ended December 31, 2020. Forthe year ended December 31, 2021, net cash provided by financing activitiesconsisted of $474 thousand in proceeds from our second draw loan under thePaycheck Protection Program, coupled with proceeds from a note payable from arelated party of $350 thousand. For the year ended December 31, 2020, net cashprovided by financing activities consisted of $654 thousand in proceeds from ourfirst draw loan under the Paycheck Protection Program.

Liquidity and Going Concern

Management continues to evaluate various financing sources and options to raiseworking capital to help fund our current research and development programs andoperations. We will need to obtain significant additional capital from sourcesincluding exercise of outstanding warrants, equity and/or debt financings,license arrangements, grants and/or collaborative research arrangements tosustain our operations and develop products. Unless we obtain additionalfinancing, we do not have sufficient cash on hand to sustain our operations atleast through one year after the issuance date. The timing and degree of anyfuture capital requirements will depend on many factors, including:

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Our failure to raise capital or enter into applicable arrangements when neededwould have a negative impact on our financial condition. Additional debtfinancing may be expensive and require us to pledge all or a substantial portionof its assets. Further, if additional funds are obtained through arrangementswith collaborative partners, these arrangements may require us to relinquishrights to some of its technologies, product candidates or products that we wouldotherwise seek to develop and commercialize on its own. If sufficient capital isnot available, we may be required to delay, reduce the scope of or eliminate oneor more of its product initiatives.

We currently have no revenue generated from our principal operations intherapeutic and clinical product development through research and developmentefforts. In addition, as we completed Phase 1 of our clinical in June 2021, wedo not anticipate significant investment in research and development effortsrelated to therapeutic and clinical product development efforts for theforeseeable future, or until such time that we initiate a Phase 2 clinicaltrial. There can be no assurance that we will be successful in maintaining ournormal operating cash flow and obtaining additional funds and that the timing ofour capital raising or future financing will result in cash flow sufficient tosustain our operations at least through one year after the issuance date.

Based on the factors above, there is substantial doubt about our ability tocontinue as a going concern. The consolidated financial statements were preparedassuming that we will continue to operate as a going concern. The consolidatedfinancial statements do not include any adjustments to reflect the possiblefuture effects on the recoverability and classification of assets or the amountsand classification of liabilities that may result from the outcome of thisuncertainty. Management's plans in regard to these matters are focused onmanaging our cash flow, the proper timing of our capital expenditures, andraising additional capital or financing in the future.

Critical Accounting Policies and Estimates

Our discussion and analysis of our financial condition and results of operationsis based upon our consolidated financial statements, which have been prepared inaccordance with accounting principles generally accepted in the United States.The preparation of these financial statements requires us to make estimates andassumptions that affect the reported amounts of assets, liabilities, revenues,expenses and related disclosures. On an on-going basis, we evaluate ourestimates and assumptions and we base our estimates on historical experience andon various other assumptions that are believed to be reasonable under thecircumstances, the results of which form the basis for making judgments aboutthe carrying values of assets and liabilities that are not readily apparent fromother sources. Actual results may differ from these estimates under differentassumptions and conditions.

Our significant accounting policies are more fully described in Note 1 to ourconsolidated financial statements included elsewhere in this Annual Report onForm 10-K. Our most critical accounting estimates include current andnon-current inventory, intangible assets, and stock-based compensation. Wereview our estimates and assumptions periodically and reflect the effects ofrevisions in the period in which they are deemed to be necessary. We believethat the following accounting policies are critical to the judgments andestimates used in preparation of our consolidated financial statements.

Intangible Assets

Our intangible assets consist of acquired patent licenses and capitalized legalfees related to the acquisition, filing, maintenance, and defense of patents andtrademarks. Amortization begins once the patent is issued by the appropriateauthoritative bodies. In the period in which a patent application is rejected orefforts to pursue the patent are abandoned, all the related accumulated costsare expensed. Our patents and other intangible assets are amortized on astraight-line basis over the shorter of the useful life of the underlyingpatent, which is generally 15 years, or when the intangible asset is rejected orabandoned. All amortization expense and impairment charges related to intangibleassets are included in general and administrative expense in our consolidatedstatements of operations.

Allowance for Excess and Obsolete Inventory

Our inventory, particularly within our biomedical market, consists of certainproducts that have a long or, when frozen, indefinite shelf life. In addition,future demand for our products is uncertain. Accordingly, at each reportingperiod, we estimate a reserve for allowance for excess and obsolete inventory.This estimate is computed using historical sales data and inventory turnoverrates, which are subjective in nature and fluctuate between periods. Theestablishment of a reserve for excess and obsolete inventory establishes a

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new cost basis in the inventory with a corresponding adjustment to cost ofsales. If we are unable to sell such inventory, any related reserves are reducedin the period of sale.

Stock-Based Compensation

We are required to measure and recognize compensation expense for allstock-based payment awards made to employees and consultants based on estimatedfair value. We estimate the fair value of stock options granted using theBlack-Scholes option-pricing model.

The determination of fair value of stock-based awards using the Black-Scholesoption-pricing model requires the use of certain estimates and subjectiveassumptions that affect the amount of stock-based compensation expenserecognized in our consolidated statements of operations. These include estimatesof the expected volatility of our stock price, expected option life, expecteddividends and the risk-free interest rate. Estimated volatility is a measure ofthe amount by which our stock price is expected to fluctuate each year duringthe expected life of the award. The expected option life is calculated using themid-point method as prescribed by accounting guidance for stock-basedcompensation. We determined expected dividend yield to be 0% given that we havenever declared or paid any cash dividends on our common stock, and we currentlydo not anticipate paying such cash dividends. The risk-free interest rate isbased upon United States Treasury securities with remaining terms similar to theexpected term of the share-based awards. If any of the assumptions used in theBlack-Scholes model change significantly, stock-based compensation expense maydiffer materially from what we have recorded in the current period.

Recently Issued Accounting Pronouncements

A description of recently issued accounting pronouncements that may potentiallyimpact our financial position and results of operations is disclosed in Note 1to our consolidated financial statements included in this Annual Report on Form10-K.

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INTERNATIONAL STEM CELL CORP MANAGEMENT'S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS (form 10-K) - Marketscreener.com

In the summer of 2015, a 7-year-old named Hassan was admitted to the burn unit of the Ruhr University Childrens Hospital in Bochum, Germany, with red, oozing wounds from head to toe.

It wasnt a fire that took his skin. It was a bacterial infection, resulting from an incurable genetic disorder. Called junctional epidermolysis bullosa, the condition deprives the skin of a protein needed to hold its layers together and leads to large, painful lesions. For kids, its often fatal. And indeed, Hassans doctors told his parents, Syrian refugees who had fled to Germany, the young boy was dying.

The doctors tried one last thing to save him. They cut out a tiny, unblistered patch of skin from the childs groin and sent it to the laboratory of Michele de Luca, an Italian stem cell expert who heads the Center for Regenerative Medicine at the University of Modena and Reggio Emilia. De Lucas team used a viral vector to ferry into Hassans skin cells a functional version of the gene LAMB3, which codes for laminin, the protein that anchors the surface of the skin to the layers below.

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Then the scientists grew the modified cells into sheets big enough for Ruhr University plastic surgeons Tobias Hirsch and Maximilian Kueckelhaus to graft onto Hassans raw, bedridden body, which they did over the course of that October, November, and the following January.

It worked better than the boys doctors could have imagined. In 2017, de Luca, Hirsch, Kueckelhaus, and their colleagues reported that Hassan was doing well, living like a normal boy in his lab-grown skin. At the time though, there was still a big question on all their minds: How long would it last? Would the transgenic stem cells keep replenishing the skin or would they sputter out? Or worse could they trigger a cascade of cancer-causing reactions?

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Today, the same team is out with an update. Five years and five months after the initial intervention, Hassan is still, for the most part, thriving in fully functional skin that has grown with the now-teenager. He is attending school, and playing sports with his friends and siblings, though he avoids swimming due to blistering in the areas that werent replaced by the lab-grown skin. One of his favorite activities is a pedal-powered go kart. There are no signs his modified stem cells have lost their steam, and no traces of tumors to be found.

The encouraging follow-up data has been instrumental in moving forward a larger clinical trial of the approach, offering hope to the 500,000 epidermolysis bullosa patients worldwide currently living without treatment options.

We were astonished by the speedy recovery, Kueckelhaus, now at University Hospital Muenster, told STAT via email. But experience from skin transplantation in other settings made him and his colleagues wary of the grafts failing as the months and years wore on. Thankfully, wrote Kueckelhaus, those fears never materialized. We are very happy to be able to prove that none of these complications appeared and the genetically modified skin remains 100% stable. The chances are good that he will be able to live a relatively normal life.

Over the last five years, Hassans team of doctors and researchers has put his new skin through a battery of tests checking it for sensitivity to hot and cold, water retention, pigmentation and hemoglobin levels, and if it had developed all the structures youd expect healthy skin to have, including sweat glands and hair follicles. Across the board, the engineered skin appeared normal, without the need for moisturizers or medical ointments. The only flaw they found was that Hassans skin wasnt as sensitive to fine touch, especially in his lower right leg. This mild neuropathy they attributed not to the graft itself, but to how that limb was prepared doctors used a more aggressive technique that might have damaged the nerves there.

The team also used molecular techniques to trace the cells theyd grown in the lab as they divided and expanded over Hassans body. They found that all the different kinds of cells composing the boys new skin were being generated by a small pool of self-renewing stem cells called holoclone-forming cells, carrying the Italian teams genetic correction.

This was quite an insight into the biology of the epidermis, said de Luca. Its an insight he expects will have huge consequences for any efforts to advance similar gene therapies for treating other diseases affecting the skin. You have to have the holoclone-forming cells in your culture if you want to have long-lasting epidermis, he said.

The approach pioneered by de Lucas team will soon be headed for its biggest clinical test yet, after nearly a decade of fits and starts. They expect to begin recruiting for a multi-center Phase 2/3 trial sometime next year.

De Luca first successfully treated a junctional EB patient in 2005. But then a change to European Union laws governing cell and gene therapies forced his team to stop work while they found ways to comply with the new rules. It took years of paperwork, building a manufacturing facility, and spinning out a small biotech company called Holostem to be ready to begin clinical research again. Hassan came along right as they were gearing up for a Phase 1 trial, but data from the boys case, which was granted approval under a compassionate use provision, convinced regulators that the cell grafts could move to larger, more pivotal trials, according to de Luca.

We didnt cure the disease, he told STAT. But the skin has been restored, basically permanently. We did not observe a single blister in five years. The wound healing is normal, the skin is robust. From this point of view, the quality of life is not even comparable to what it was before.

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Syrian refugee is thriving five years after last-gasp gene therapy - STAT - STAT

Rockville, Md. (December 8, 2021)Using pulsed laser light under tightly controlled conditions, researchers were able to seein the earlobe skin of anesthetized mice the sequence of cellular events that trigger the beneficial effects of intra-epidermal focal laser-based therapy. The findings are published in a new study in the journal Function. Cells in this layer, called basal keratinocytes, are of the stem cell moiety and absolutely crucial for the continuous renewal of the skin, which occurs throughout the life span. By studying the response of the skin in real time with sophisticated imaging technology, physiologists discovered the sole cell hit by the laser became the epicenter of a wave that spread radially from cell to cell. The wave then rippled in the concentration of ionized calcium (Ca2+) within the affected cells. Ca2+ waves are known to convey messages or instructions that are able to modify cell behavior, including the possibility to modify gene expression.

These results may have significant implications for future device/procedure development, said Fabio Mammano, PhD, study co-researcher from the University of Padova in Italy.They may lead to better dosage and timing of the laser pulses, wavelength optimization and, importantly, selection and/or discovery of drugs that interfere with thesignalingpathways we have identified to further enhance the production of extracellular matrix and collagen, as well as the replacement of scar tissue with fresh epidermal and dermal cellular components.

Read the full article, Calcium signaling in the photodamaged skin: in vivo experiments and mathematical modeling, published ahead of print in Function. Contact APS Media Relations or call 301.634.7314 to schedule an interview with a member of the research team.

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Benefits of Pulsed Laser-based Skin Therapy - Newswise

Stem cell therapy, sometimes called regenerative medicine, is one of the most exciting areas of the life sciences sector right now.

Since the pandemic, the sector has emerged into the publics spotlight with new developments in mRNA-based vaccines and therapies.

Nasdaq is the obvious breeding ground for world-class stem cell companies with the likes of Moderna and BioNTech, and lesser known names like Anavex and Enochian.

In Australia, Mesoblast (ASX:MSB) has long been the local poster child for the regenerative medicine industry.

Mesoblast has developed a platform of innovative cellular medicines, but the company has struggled since the FDA rejected its drug in October last year.

Now, other ASX companies like Cynata Therapeutics (ASX:CYP)are making rapid progress to take over the mantle from MSB in this hot field.

Cynata is developing a mesenchymal stem cells (or MSC) technology, which it says has huge therapeutic potential for numerous unmet medical needs.

This includes asthma, heart attack, sepsis, and acute respiratory distress syndrome (ARDS), which all add up to a market opportunity worth $46bn, says the company.

According to CEO Dr Ross Macdonald, who spoke to Stockhead today, MSC is the hottest segment of stem cell therapy at the moment, and has gained a lot of attention recently.

There is a huge interest, and theres been more than 1000 clinical trials conducted around the world using MSC, Dr Macdonald told Stockhead.

He explains that the humans immune system controls many of the bodys functions responsible for repairing tissue after injury or disease, and defending against invading germs like viruses or bacteria.

And just like an orchestral conductor, MSC seems to be playing a central role in that coordination within our immune system.

We now have a firm understanding of how those cells coordinate the bodys responses, and can use that knowledge to enhance those processes that they control, Dr Macdonald explained.

In short, MSC therapies work by expressing a variety of chemokines and cytokines that aid in repair of degraded tissue, restoration of normal tissue metabolism and, most importantly, counteracting inflammation.

And because MSCs play that co-ordination role within the immune system, they can be used to treat different diseases.

However theres one big problem with cell-based therapies, and its not to do with the safety and efficacy.

Its how to manufacture these products on a mass scale, that is the greatest challenge right now, says Dr Macdonald.

Unlike aspirin where it can be synthesised in a chemical lab and produced in bulk, manufacturing a living drug like a cell is a whole lot more complicated.

But that big challenge is the exact area of strength and competitive advantage that Cynata has, Dr Macdonald told Stockhead.

He says Cynata has a technology platform which allows it to manufacture essentially limitless quantities of MSCs, consistently and economically.

Dr Macdonald explains there are two approaches to using cell therapy, the autologous and the allogeneic approach.

The autologous approach is where the patient themselves serves as their own donor.

This is obviously bespoke and inefficient, because the drug can only be manufactured for that one patient, and is obviously not an industrialised process, he said.

But by taking an allogeneic approach, Cynata has the ability to start with a one time donation of cells from one single donor.

Well never have to go back to that human donor ever again, so our process of producing cells has become a very much more typical industrialised process.

The company has a patent for this, with two clinical trials underway and two more under preparation.

A Phase 3 clinical trial for osteoarthritis which is funded by a NHMRC grant has progressed the furthest, while a Phase 2 trial in COVID-19 is ongoing.

Meanwhile a Phase 1 study in GvHD, which was published in prestigious journal Nature Medicine, is probably the closest to commercialisation according to Dr Macdonald.

GvHD is a challenging disease which occurs in patients who have had a bone marrow transplant as part of their chemotherapy treatment for cancer.

Chemo is still very much a sledgehammer therapy where you use very toxic drugs that do kill the cancer cells, but they also kill the surrounding healthy cells that grow hair and bone marrow.

Unfortunately for many patients, the bone marrow transplant reacts against their body and starts to attack all of the tissues in the body, and its ultimately fatal.

Its a horrible death, destroying the lungs, liver, intestines and the skin, Macdonald explains.

Cynatas MSC therapy has been shown to reset that reaction, so the patient can recover from the GvHD, and also recover from their underlying cancer.

With all these clinical trials concurrently under way, Macdonald believes there is a clear significant upside potential for Cynata, particularly given its small market cap of $70m compared to other similar plays like Mesoblast ($1 billion market cap).

Osteopore (ASX:OSX) focuses in bones and specialises in the production of 3D printed bioresorbable implants that are used in surgical procedures to assist with the natural stages of bone healing.

The 3D bio-printer makes a scaffold that mimics bone, with a patented micro-architecture which traps the patients own stem cells.

Orthocell (ASX:OCC) develops collagen medical devices and cellular therapies for the repair and regeneration of human tendons, bone, nerve and cartilage defects.

Its flagship product, the CelGro, is a naturally derived collagen medical device for tissue repair.

Aroa Biosurgery (ASX:ARX) develops FDA-approved medical devices for wounds and tissue repair using its extracellular matrix (ECM) technology, mainly in the United States.

Recent study shows 100% success rates from the use of its Myriad product when patients underwent surgical reconstruction of exposed vital structures such as bone and tendon.

Regeneus (ASX:RGS) Progenza is a cellular therapy targeting pain and inflammation which uses Secretome to improve not only the resident tissue, but the MSCs themselves.

It fills a gap in the current treatment market for osteoarthritis, by providing disease modification and pain relief to address patient symptoms.

Anteris Technologies (ASX:AVR) claims that its Adapt Technology is the first and only bio-scaffold technology that completely re-engineers xenograft tissue into a pure collagen scaffold.

A recent study indicated that Adapt-treated tissue has superior anti-calcification attributes compared with tissues used in competitor valves.

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Mesoblast has long been the one poster child for stem cell therapy. Now Cynata and other ASX stocks have e ... - Stockhead

Inbreeding and wild tigers at risk of extinction

As habitat fragmentation increases worldwide, wild animal populations are shrinking and becoming more isolated, thus facing a heightened risk of inbreeding and extinction. The extent to which the viability of small, isolated populations could be improved by purging deleterious alleles through natural selection is unclear. Anubhab Khan et al. analyzed whole-genome sequences from 57 wild Bengal tigers from either a small, isolated population or large, connected populations in India. The results revealed evidence of partial purging of highly detrimental variants across populations. However, the small, isolated population showed genomic signs of greater inbreeding and a higher overall frequency of deleterious alleles, compared with two large populations. On average, pairs of individuals from the small, isolated population shared approximately 40% of their genomes in tracts at least 1 megabase long, whereas pairs from the large, connected populations shared approximately 1525% of their genomes. Together, the findings suggest that purging may not eliminate all detrimental alleles and inbreeding-associated fitness costs in small, isolated populations. According to the authors, the findings highlight the need for genetic rescue strategies that enhance the fitness of inbred populations by decreasing the frequency of harmful mutations and increasing genetic variation. J.W.

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In This Issue - pnas.org

Every year, African lungfish survive to the dry seasons in Africa by creating a cocoon that allows them to live on land for months or even years, until water returns following long periods of heat and drought. This cocoon, in which the lungfish is suspended in a prolonged state of aestivation, or torpor or dormancy, is a great way to prevent water loss, as many others have reported while studying aestivating frogs and other amphibians.

But researchers at The University of New Mexico are trying to find out how these animals survive pathogen and predator attacks when they are in this dormant, vulnerable state. The research could shed light on treating inflammatory diseases and investigating immune systems.

Irene Salinas

A study titled The lungfish cocoon is a living tissue with antimicrobial functions, recently published in Science Advances, was led by Associate Professor of Biology Irene Salinas and her team. The study was led by Ph.D. candidate at the Salinas lab Ryan Heimroth, who graduated in late 2020 and is now a postdoctoral researcher at Emory University. Key contributions were made by postdoctoral researchers in the Salinas lab, Elisa Casadei and Ottavia Benedicenti. Collaborators outside UNM include Chris Amemiya at University of California, Merced, and Pilar Muoz at Universidad de Murcia, Spain.

This study reveals the extraordinary adaptations of the immune system of African lungfish which allow this species to survive the harsh aestivation periods every year. Salinas said this is the most fascinating and fun project she has ever worked on in her entire career as an evolutionary immunologist.

We started this project in 2017 and we knew it was going to be exciting but we never thought that the results were going to be so astounding, she said. When we started this project, we thought the cocoon is formed by mucosal secretions that dry up around the lungfish body, but when we looked closer we realized the cocoon was actually full of cells and the cells were alive. Further experiments revealed that the cocoon is formed and shedding of layer after layer of skin epidermis, thanks to the large numbers of dermal stem cells that lungfish.

We know very little about the immune system of lungfish, Salinas continued, but very old studies from the 1930s gave the researchers some hints. These pioneer studies told them that the lungfish produces unusually large numbers of immune cells called granulocytes. Granulocytes are very important first lines of defense against pathogens and the first cells to migrate to sites of inflammation.

But why do lungfish have so many? Why is that so important? The team looked carefully at how these granulocytes changed when they aestivated lungfish in the laboratory. Granulocytes left their tissue reservoirs, traveled in the blood, and flooded the skin of aestivated animals. This is a hallmark of inflammation, very similar to what happens in the human gut and skin when it is inflamed. Lungfish do it to themselves as soon as they sense that the environment is unfavorable.

So what do these cells do when they get to the skin? Well, they leave the skin and become part of the cocoon, Salinas said. Yes, the cocoon is now not only a layer of mucus that prevents water loss but an immunological shield, full of granulocytes, potent antimicrobial soldiers that can trap and kill pathogens.

Once the researchers saw the granulocytes in the cocoon they were sure the cocoon had immunological functions, Salinas said. Following a series of investigative procedures, they concluded that the cocoon acts as an extracorporeal bacterial trapping device, the lungfish body staying healthy during aestivation, the cocoon fighting bacteria outside the body.

The key to the cocoon antimicrobial function is that granulocytes have fancy magic tricks under their hats, Salinas said. In a process known as extracellular trap formation, granulocyte extrude their DNA along with many antimicrobial compounds that decorate the DNA forming these traps. The lungfish cocoon was full of granulocytes that were caught in the process of making extracellular traps, explaining why bacteria did not penetrate into the aestivating lungfish body.

The team set experiments to answer what happens if a lungfish cocoon cannot make extracellular traps and found that extracellular DNA was essential for lungfish to stay healthy during the aestivation process.

While these findings reveal very fundamental immunological adaptation of a vertebrate animal with extreme biology, they may also illuminate key aspects of maladaptive immune responses that occur during inflammatory diseases at mucosal barriers.

Clearly, lungfish are very good at injuring their skin and sef-inflicting inflammation, Salinas said, yet when water returns, they are able to regenerate their tissues and swim back in the water as if nothing ever happened.

These animals, therefore, may keep many secrets that we could use in the future to treat inflammatory diseases, Salinas said, adding that she also wants to advocate for the investigation of immune systems in non-traditional models, such as the lungfish.

This work was generously supported by the National Science Foundation award #1938816. The team hopes to continue to investigate the immune system of this fascinating animal in the next few years, Salinas noted.

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UNM research team finds lungfish cocoon is living tissue with antimicrobial functions - UNM Newsroom

Using a new mini-brain model, a large team of researchers were able to demonstrate the damaging changes that occur in brain cells of people with frontotemporal dementia (FTD). Published in Cell on Aug. 19, the findings show a clear sequence of damaging events that eventually lead to cell death and provide potential pathways to develop and test treatments for this disease.

FTD is a form of dementia that can cause behavioral changes, trouble with communication, and movement problems. These symptoms result from brain cells, or neurons, dying in certain parts of the brain. Some FTD cases result from inheriting a mutated version of the MAPT gene, which causes abnormalities in a protein called tau.

To study how this mutation causes neurons to die, researchers created a new model that allows them to see the progression of events that leads to cell death. The study is the result of a large collaboration among researchers from the Icahn School of Medicine at Mount Sinai, Massachusetts General Hospital, Harvard Medical School, the Neural Stem Cell Institute, University of Southern California, Amgen Research, and Washington University in St. Louis.

In the study, researchers took advantage of technology that allows skin cells to turn back into stem cells. Humans begin fetal development as one cell, which divides to become a handful of cells, and eventually becomes the whole body. These early cells, called stem cells, are able to become any type of cell in the body. Starting with skin cells donated by people who carry a MAPT gene mutation that causes FTD, the scientists turned back the developmental clock and reverted those skin cells into stem cells. Then the researchers grew these stem cells into neurons and assembled those neurons into mini-brain models, looking for symptoms of cellular disease along the way.

By studying these FTD mini-brain models, the scientists discovered a sequence of events that goes wrong in neurons and eventually causes them to die. The neurons in the FTD mini-brain models were already showing signs of stress two months after development. At four months, researchers observed that tau protein was building up in the neurons and that the waste management systems that would normally help clear the build-up had started to fail.

In addition, the scientists discovered that the neurons had harmful changes in splicing a process by which the cell chooses which parts of a gene will be included in the protein it encodes. The faulty splicing was caused by an increase in the amount of a protein called ELAVL4, which regulates splicing of genes involved in communication between neurons. The splicing changes eventually caused the neurons to have too many glutamate receptors proteins that allow the neuron to hear an incoming chemical message. At six months, there were so many receptors that just getting messages from other neurons was overwhelming and toxic. Finally, the researchers tested a drug called apilimod that reduces the number of receptors present at connections between neurons and found that this could stop neurons from dying in the FTD mini-brain models.

The researchers noted some limitations; namely, that the mini-brain models do not have the helper cells, called glia, that are present in actual brains and provide support for neurons to function and communicate. In the future, they would like to explore how the helper cells affect the progression of disease in the neurons. Overall, the study provides critical insights into the events that cause neurons to die in people with genetically inherited FTD. These insights will help scientists to develop and test new therapeutics for the disease.

This research was supported in part by NIH grants R01AG056293 and F31NS117075.

These activities relate to NIHs AD+ADRD Research Implementation Milestone 2.N, Clarify unique and converging cellular mechanisms related to tau pathogenesis, C9orf72 hexanucleotide repeat expansions, GRN mutations, and other targets and pathways contributing to FTD neurodegeneration.

Reference: Bowles KR, et al. ELAVL4, splicing, and glutamatergic dysfunction precede neuron loss in MAPT mutation cerebral organoids. Cell. 2021;184(17):4547-4563. doi: 10.1016/j.cell.2021.07.003.

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Mini-brain model of frontotemporal dementia demonstrates the stages of dysfunction that lead to cell death - National Institute on Aging

Dr. Green dedicated his career to furthering our understanding of skin regeneration and improving the outcomes for patients, Dr. Morgan said. I am honored not only to build on his work in helping improve the lives of patients, but to do so together with Shriners Hospitals for Children.

BOSTON (PRWEB) November 01, 2021

Shriners Childrens is pleased to announce that a cutting-edge gene and stem cell therapy research program to cure the rare skin blistering disorder is to be supported by the Howard Green Center for Childrens Skin Health & Research at Shriners Hospitals for Children Boston.

The lead scientist is Dr. Jeffrey Morgan who has proven track record of successful innovation and leadership skills. Dr. Morgan will guide this program as it pursues its goal of improving the outcomes and lives of patients with burns, skin disorders and dermatological conditions. The expert co-investigators on the research project are Robert Sheridan M.D., Mehmet Toner Ph.D., and Martin Yarmush M.D., Ph.D., all at Massachusetts General Hospital (MGH), Harvard Medical School (HMS) and Shriners Childrens Boston.

Dr. Morgan has extensive experience in genetically engineering skin to treat various genetic disorders or to deliver local wound healing factors. His interdisciplinary research has produced 110 publications in high-impact, peer-reviewed scientific journals. Working in translation and commercialization of technologies, Dr. Morgan is an inventor on thirteen issued patents and was elected a Fellow of the National Academy of Inventors. Innovations developed in his laboratories are distributed worldwide. Dr. Morgan has served in a number of leadership positions in academia as well as start-up companies.

Dr. Morgan trained at Massachusetts Institute of technology with Howard Green, M.D. Dr. Green was the first to grow skin grafts using a patients own cells, one of the earliest examples of stem cell therapy. The first grafts from cultured skin were used to treat two patients with life threatening burns at Shriners Hospitals for Children Boston in the early 1980s, cementing the impact of Dr. Greens discovery as well as his bond with Shriners Hospitals for Children.

Dr. Green dedicated his career to furthering our understanding of skin regeneration and improving the outcomes for patients, Dr. Morgan said. I am honored not only to build on his work in helping improve the lives of patients, but to do so together with Shriners Hospitals for Children.

Dr. Morgans appointment as principal investigator will help the Howard Green Center for Childrens Skin Health & Research take the next step in caring for patients with devastating skin injuries and conditions, said Jerry G. Gantt, Chairman of the Board of Trustees of Shriners Hospitals for Children. Dr. Morgans leadership in the field and longtime connection with Dr. Howard Green make him a natural choice to lead the research project, and we are honored to have him as an important part of our Shriners Childrens family.

About the Howard Green Center for Childrens Skin Health & Research at Shriners Childrens BostonFounded in 2016, the Howard Green Center for Childrens Skin Health and Research at Shriners Hospitals for Children Boston is a first-of-its kind center dedicated to advancing the field of regenerative medicine. The mission is to engage in translational research projects that work hand-in-hand with clinical practice to move regenerative medicine along the discovery continuum to bring new treatments to children more quickly. The ultimate goal is to further improve the outcomes and lives of patients with burns, skin disorders and dermatological conditions by providing world-class care regardless of the families ability to pay.

The Center is the vision of Dr. Green and his family. By making a generous and transformational gift to Shriners Hospitals for Children Boston, Mrs. Rosine Kauffmann Green ensured her late husbands work would continue on and help children in Boston and around the world.

About Shriners Childrens Shriners Childrens is changing lives every day through innovative pediatric specialty care, world-class research and outstanding medical education. Our health care system provides care for children with orthopedic conditions, burns, spinal cord injuries, and cleft lip and palate. All care and services are provided regardless of the families ability to pay. Since opening its first location in 1922, the health care system has treated more than 1.5 million children. To learn more, please visit shrinershospitalsforchildren.org.Media Contact:Mel Bower, Shriners Hospitals for Children813-281-8643, mbower@shrinenet.org

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A major research project to advance regenerative therapy for epidermolysis bullosa (EB) using transgenic stem cells - PR Web

Peptides don't get talked about nearly enough as some other ingredients, like hyaluronic acid, vitamin C, and retinol, but their benefits are bountiful and play a key role in improving the elasticity and plumpness of your skin. As we previously reported, peptides essentially act as tiny messengers that send messages directly to our skin cells to promote better communication. (If only they could perform the same task to better our relationships we kid.)

At their core, peptides are "chains of different types of amino acids, like glycine, arginine, histidine, etc.," David Kim, M.D., a board-certified dermatologist in New York City explains to Allure. "Peptides in skin-care products are designed to boost and replenish amino acids, which are the building blocks for collagen production." Since amino acids are the smallest unit of a protein, peptides are able to mimic another type of protein, collagen. And compared to topical collagen, peptides also have a much smaller particle size and can actually be absorbed into your skin.

"By boosting collagen production, [peptides] can help reduce the appearance of fine lines and make the skin firmer," Dr. Kim says, adding that everyone can incorporate and benefit from using the powerhouse ingredient in their routines. To that end, he says that you shouldn't experience any side effects while using peptides. "If someone has a [negative] reaction, it's most likely from the preservatives, other chemicals, or essential oils in the formula, not the peptides," Dr. Kim explains.

Mature skin can definitely benefit from peptides since, unfortunately, our bodies start to produce less and less collagen as we age. And, not to mention, the quality of said collagen also decreases over time, board-certified dermatologist Corey L. Hartman, M.D. who is based in Birmingham, Alabama, explained to us. As a result, wrinkles start to form and skin begins to sag.

Common categories of peptides consist of signal, carrier, enzyme-inhibitor, and neurotransmitter-inhibitor depending on how they work. For example, copper peptides activate wound healing, which, in turn, stimulates collagen production. But that's a bit hard to remember, especially considering that labs and brands can and do trademark their own peptide complexes.

As a consumer, you'll often find "peptide" placed front and center on the actual product packaging, you can also look out for ingredients like dipeptide, tripeptide, and hexapeptide. It's not uncommon to see multiple peptides strung together to maximum their collagen-boosting benefits, like Paula's Choice Peptide Booster and The Ordinary "Buffet."

To help you sort out the vast market, we asked dermatologists and our very own Allure editors to recommend their favorite peptide skin-care products, so you can be well on your way to achieving smoother, firmer skin.

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15 Best Peptide Skin-Care Products 2021 for Smoother, Firmer, and Plumper Skin - Allure

Our Need For Things Lab-Grown

What was once something of the movies objects forming themselves in thin air is real now. Various things can be grown in a laboratory setting, some even on a large scale for commercial distribution. This technology could be a big part of the solution to establish sustainable societies. At the moment, we harvest organs from the deceased, rear animals for meat and dairy, destroy forests by cutting down trees for wood, mine the earth for diamonds, and the list goes on. All these things can already be lab-made or are on the brink of reality.

Once these staples of society can be mass-made affordably, they could supply the world while minimally impacting the natural environment. Acres of land wouldnt need to be used for food and building materials, meaning deforestation can cease, for starters. Looking at lab-grown meats alone: they require 99% less land than traditionally farmed meats, generate up to 96% fewer emissions, use up to 96% less water, and no animals need to be slaughtered in the process.

Naturally, there will be short-term disruptions, particularly job-related. For example, eco-friendly agriculture will mean fewer farms and agriculture jobs. But new employment opportunities will emerge in the scientific and technical fields related to lab-grown foods.

Whats the difference between 3D printing (additive manufacturing) and lab-grown, you may be wondering? 3D printing uses material as ink anything from plastic to cellular material whereas lab-grown materials start off as a bit of material that multiplies on its own, replicating natural processes. Thus, lab-grown material has the same cellular structure as the naturally occurring material and mimics the natural formation process but within a much shorter period.

In the future, we are bound to see various lab-grown breakthroughs coming from the medical field. Eventually, there should be alternative sources for organs and blood cultured from stem cells. In addition, there will likely be lab-produced medicines (lotions, ointments, balms, nutraceuticals, energy drinks, etc.), breast milk, and more.

Scientists are well on the way to functioning full-sized organs, with several innovations in fully functional mini-organs, or organoids, making headlines in recent years. For now, these organoids are tools for testing new drugs and studying human diseases. But soon enough, these research teams will take the technology to the next level and develop organs that can be used for implantation when someone needs an organ replacement. So far, the brain, liver, lungs, thymus, heart, blood, and blood vessels are among the growing list of lab-grown medical accomplishments.

A team of scientists from the University of Pittsburgh managed to grow miniature human livers using induced pluripotent stem cells (IPSCs) made from human skin cells. Meaning, in the far future, someone needing a liver transplant could have the organ grown from their own skin cells! This method may even reduce the chances of a patients immune system rejecting the new tissue because it would recognize the cells as self. Whats more, their lab-grown livers matured in under a month compared to two years in a natural environment.

The scientists tested their fully-functional mini-livers by transplanting them into rats. In this proof-of-concept study, the lab-made organs survived for four days inside their animal hosts, secreting bile acids and urea like a healthy liver would.

A research team led by the University Hospital Dsseldorf induced pluripotent stem cells (iPSCs) to grow into pea-sized brain organoids with rudimentary eye structures that sense light and send signals to the rest of the brain. They used skin cells taken from adult donors, reverted them back into stem cells, and placed them into a culture mimicking a developing brains environment, which encourages them to form specific brain cells. Their mini-brains grew optic cups, vision structures of the eye found where the optic nerve and retina meet. The cups even grew symmetrically, as eyes would, and were functional!

Jay Gopalakrishnan, a senior author of the study, said:

Our work highlights the remarkable ability of brain organoids to generate primitive sensory structures that are light sensitive and harbor cell types similar to those found in the body. These organoids can help to study brain-eye interactions during embryo development, model congenital retinal disorders, and generate patient-specific retinal cell types for personalized drug testing and transplantation therapies.

This achievement is the first time an in vitro system shows nerve fibers of retinal ganglion cells reaching out to connect with their brain target an essential aspect of the mammalian brain.

Scientists from Michigan State University developed functional miniature human heart models grown from stem cells complete with all primary heart cell types and with functioning chambers and vascular tissue. The models could help researchers better understand how hearts develop and provide an ethical platform for treating disease and testing drugs or new treatments.

The teams lab-grown mini hearts follow the fetal development of a human heart, offering a new view into that process. The organoids start beating by day six, and they grow into spheres approximately 1 mm (0.4 in) wide, with all significant cardiac cell types and multiple internal chambers by day 15.

Aside from research purposes, full-sized lab-grown hearts could solve the shortage problem of hearts the world faces today. More than 25 million people suffer heart failure each year. In the United States, approximately 2,500 of the 4,000 people in line for heart transplants receive them. That means almost 50% of the people needing a new heart to keep them alive wont get it.

Unlimited supplies of blood for transfusions are possible with lab-growing technology. Blood has been challenging to grow in the lab. However, real breakthroughs in creating artificial blood have sprung up!

A couple of years ago, Japanese researchers developed universal artificial blood that worked for all blood types. It even has a shelf life of one year stored at room temperature, therefore eliminating the problem of identifying blood type and storage simultaneously.

Like that wasnt impressive enough, last year, a team of scientists from the South China University of Technology, the University of New Mexico, and Sandia National Laboratories created artificial red blood cells (RBCs) with more potential capabilities than real ones! The synthetic RBCs mimic the properties of natural ones such as oxygen transport, flexibility, and long circulation times with the addition of a few new tricks up their sleeves, such as toxin detection, magnetic targeting, and therapeutic drug delivery. In addition, blood contains platelets and red blood cells, so these new cells could be used to make superior artificial blood.

Researchers from the University of British Columbia successfully coaxed stem cells to grow into human blood vessels. The thing that is so remarkable about this study is that the system of blood vessels grown in the lab is virtually identical to the ones currently transporting blood throughout the body. They are using this now to generate new leads in diabetes treatment. They put the lab-grown blood vessels in a petri dish designed to mimic a diabetic environment.

The global demand for meat and dairy is expected to rise by almost 90% over the next 30 years, regardless of the need to cut back on meat consumption. The risk of environmental damage and the rising food demand itself is a problem many have recently addressed. Thats why companies worldwide are on the verge of scaling up all sorts of lab processes to produce various food items, including steaks, chicken, cheese, milk, ice cream, fruits, and more.

Thinktank RethinkX even published research suggesting that proteins from precision fermentation (lab-grown protein using microbes) will be about ten times cheaper than animal protein by 2035, resulting in a collapse of the livestock industry. It says the new food economy will subsequently:

replace an extravagantly inefficient system that requires enormous quantities of inputs and produces considerable amounts of waste with one that is precise, targeted, and tractable. [Using tiny land areas, with a massively reduced requirement for water and nutrients, it] presents the most significant opportunity for environmental restoration in human historyFarm-free food offers hope where hope is missing. We will soon be able to feed the world without devouring it.

The worlds pace of meat consumption is placing a significant strain on the environment. Many studies show that eating less meat is just as crucial to slowing down global warming as using solar panels and zero-emissions vehicles. Unfortunately, animal farming generates an obscene amount of greenhouse gas emissions. Yet again, scientists come to the rescue, working diligently to fix this situation.

Over a decade ago, researchers created something akin to ground beef, but the complex structure of steak didnt happen until recently, with Aleph Farms debuting its thick-cut rib-eye steak in 2018. Furthermore, that first burger cost around US$345,000, but now the price has dropped dramatically to the point that lab-grown chicken is to be commercially produced and hit grocery store shelves as of this year.

SuperMeat, Eat Just, and Aleph Farms are todays most prominent startups working on getting lab-grown meats to people looking to lower their carbon and environmental footprints. In addition, their products are made from actual animal cells, so theyre real meat, but no animals had to be hurt or killed.

Speaking of Aleph Farms, the company also grew meat in space to show that it can even be done in a zero-gravity environment with limited resources.

Aside from Aleph Farms figuring out how to make steak like an authentic steak, a group of Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) researchers also devised a solution to the texture challenge. First, they made edible gelatin scaffolds that have the texture and consistency of real meat. Then, they grew rabbit and cow muscle cells on this scaffolding. The research demonstrates how realistic meat products are possible!

Parker and his Disease Biophysics Group developed a technique to produce the scaffolding. Its a fiber-production system inspired by cotton candy known as immersion Rotary Jet-Spinning (iRJS). It enabled the team to spin long nanofibers of a specific shape and size using centrifugal force. So, they spun food-safe gelatin fibers, creating the base upon which cells could grow.

Natural muscle tissue is composed of an extracellular matrix, which is the glue that holds the tissue together. As a result, it contributes to the texture of the meat. The spun gelatin fibers mimicked this extracellular matrix and provided the texture to make the lab-grown meat realistic. When the team seeded the fibers with animal (rabbit and cow) muscle cells, they anchored to the gelatin scaffolding and grew in long, thin structures, similar to real meat.

Meanwhile, Boston College developed a new, even greener technology that uses the skeleton of spinach leaves to support bovine animal protein growth. However, animal products arent eliminated from the process entirely. For example, lab-grown steak and chicken are created by painlessly harvesting muscle cells from a living cow, subsequently fed and nurtured to multiply and develop muscle tissue. But for this to have the same texture as real meat, the cells need structural support to flourish and are therefore placed in a scaffold.

Singapore is leading the way, becoming the first country in the world to approve the sale of Eat Justs cultured chicken. The company will start by selling nuggets at a restaurant. Meanwhile, SuperMeat has been handing out lab-grown chicken burgers in Israel for free. Theyre aiming to gain public acceptance of the idea.

The cultured chicken starts as a tiny number of harvested cells. Those cells are put into a bioreactor and fed the same nutrients the living animal would consume to grow. The cells multiply and turn into an edible portion of cultured chicken meat. The meats composition is identical to that of real chicken and offers the same nutritional value. And its cleaner because its antibiotic-free!

Labs are manufacturing dairy products by utilizing the fermentation process of living microbes to produce dairy proteins like whey and casein. These proteins are then used to make dairy products like butter, cheese, and ice cream. Two leading companies in this category are Imagindairy and Perfect Day, which already have several products on supermarket shelves in the United States.

Researchers havent figured out how to make fruits and vegetables yet, but a team is perfecting a cell cultivation process that generates plant biomass. The stuff tastes like the natural-grown product from which the cells were obtained and even exceeded its nutritional properties. Although, the texture of the biomass is different. For example, an apple isnt a solid apple akin to one grown from a tree. Instead, its like applesauce.

Lab-produced materials Including wood, diamonds, leather, glass, clothing, crystals, gels, cardboard, and plastics for making objects are either under development or already available. Many materials need to be taken from nature mined from the earth or cut down from forests. If they can be made in a lab instead, then people could leave nature alone!

A recent project led by a Ph.D. student at MIT paves the way for lab-grown wood one of the worlds most vital resources used to make paper, build houses, heat buildings, and so much more. The process begins with live plant cells cultivated in a growth medium coaxed using plant hormones to become wood-like structures. Next, a gel matrix is used to guide the shape of the cellular growth, and controlling the levels of plant hormones regulates the structural characteristics. Therefore, the technology could grow anything from tables and chairs to doors to boats and so on.

The environmental and socio-economic impact of traditionally mined diamonds has been exposed in recent years, and as awareness grows, the rising popularity of lab-grown diamonds does too. Mined diamonds are linked to bloody conflicts, and their excavation produces carbon emissions, requires substantial water use, and causes severe land disturbances.

Research has found that 1,000 tons of earth have to be shifted, 3,890 liters or more of water is used, and 108kg of carbon is emitted per one-carat stone produced. In addition, the traditional diamond mining industry causes irreversible damage to the environment, hence why, a decade ago, researchers started experimenting with how to grow them in the lab. Its been a feat a long time in the making, but we finally have lab-grown diamonds available for eco-conscious consumers to buy.

Diamonds are made of pure carbon. It takes extreme heat and pressure for carbon to crystalize. In nature, this happens hundreds of miles beneath the Earths surface. The ones being mined were shot out by a volcano millions of years ago. So how have scientists managed to hack such an intense and time-consuming process?

They began by investigating the mechanisms behind the diamond formation, zooming in at the atomic level. This led to the invention of a novel technology that utilizes the process of HPHT (high pressure, high temperature) to mimic the natural atmospheric conditions of diamond formation. Labs can use it to replicate the process and turn pure carbon into diamonds in 2-6 weeks.

Lab-grown gems are eco-friendly rocks, especially when theyre made entirely from the sky, like SkyDiamonds. Even the electricity used to grow its stones is from renewables, so theyll indeed be the worlds first zero-impact diamonds.

But how are the diamonds created out of thin air? They are made of carbon from the sky and rainwater. The sky mining facility is in Stroud. Energy is sourced from wind and sunlight. The CO2 is sourced directly from the air. Hydrogen is produced by splitting rainwater molecules in an electrolysis machine using renewable energy. The captured carbon and hydrogen are then used to make methane, used to grow the diamonds. The final product is a diamond anatomically identical to those mined from the ground. It is even accredited, fully certified, and graded by the International Gemological Institute.

Another company, Climeworks, is also making diamonds using carbon sucked from the sky. However, SkyDiamonds takes it a step forward by using rainwater and sunshine in the process.

The last lab-grown object were going to discuss is not something in the works, but an idea a fantastic and outlandish one thats jumping far into the future but was thought up in 2010 by Mercedes Benz. The luxury car companys ambitious BIOME idea shows just how wild imagination can get with lab-grown technology. It envisions a day when it can grow an entire supercar from scratch.

Mercedes-Benz explained when launching the concept:

The interior of the BIOME grows from the DNA in the Mercedes star on the front of the vehicle, while the exterior grows from the star on the rear. The Mercedes star is genetically engineered in each case to accommodate specific customer requirements, and the vehicle grows when the genetic code is combined with the seed capsule. The wheels are grown from four separate seeds.

This list of lab-grown possibilities is just the tip of the iceberg! Other materials in the pipeline include leather, chocolate, and silk. This intelligent technology can make anything a scientist can dream up! The only limit is the imagination and dedication of brilliant people.

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Lab-Growing Everything Might Be The Only Way To Attain A Sustainable World - Intelligent Living

By Suzy Cohen

I was talking with a friend the other day who said she is experiencing hair loss, and that it is very disappointing to her because it appears to be getting worse. She was leaning on me for advice because she said,I cant look in the mirror anymore.

She has tried all the expensive shampoos, and color treatments, she has asked her doctor, and she has finally retreated to the reality of losing her hair, when she is still a very pretty woman in her mid 70s. Basically, shes given up hope for restoration.

Within minutes I was able to discern the problem for her, and arm her with information to regrow her hair.

Todays article is to help you too. Id like to show you some more possible causes for your own hair loss in case youve given up hope yourself. Its not always because of advancing age, although that is one obvious reason.

An estimated 100 hairs are shed every day! Thats hard to believe, but its true. If youre not growing new hairs, the hair loss becomes more evident. So hair loss and hair growth are two different things. You cant stop the shedding, thats natural, but you do have some control over new hair growth. You also have a little control over factors that lead to excessive hair shedding, maybe not stem cells but certainly other factors. The stem cell theory is brand new!

Stem cell studies suggest that the 1.5 grams of dead material that we shed daily (about 500 million cells) is replaced by new stem cells, and our stem cells are compromised, and lower in number as we age. The see-saw of hair growth to hair shedding tilts in favor of hair loss with higher age. But as you will soon see, my article will show what else accelerates the hair loss.

My point is that its not always about a reduction in hormones due to menopause, although that is another obvious reason. There are many common reasons that physicians can find and help you with. Im not dealing with the easy, obvious reasons for hair loss today. I want to tackle the harder, overlooked causes.

I think millions of you reading this today will benefit. At the end of the day, I feel like this: If you cant figure out the root cause of the hair loss, you are never going to solve it! So I want to help you determine the root cause because hair is important to many people. The loss of it makes people avoid looking in the mirror.

Statin Use.

People with elevated cholesterol sometimes take statin medications such as atorvastatin to help improve their ratios. A well-documented side effect of this category of medications is reduced production of thyroid hormone. And that leads to hair loss. This was exactly the problem with my friend the other day she told me she had been on a statin drug for about 2 or 3 years, and thats when her problem began. Statins, through their drug mugging effect, lead to reduced hair growth and extra shedding.

The fix for statins:Since you cant discontinue your medication, the fix for this problem is simple. Id suggest you talk to your physician and get a prescription for Cytomel or Compounded T3 timed release, or the generic drug Liothyronine which is a biologically active form of thyroid hormone. All of these require a prescription. You could also try a good thyroid supplement to support thyroid hormone synthesis. You may also want to look into one particular mineral called selenium.

Selenium supplementation all by itself may be useful because statins are a drug mugger of selenium, and without that mineral, you could become hypothyroid. For that matter, coffee is a drug mugger of iron and magnesium which also leads to hypothyroidism. You can watch my shortVIDEOabout that.

Im not recommending all of the above options, Im just giving you choices to consider. Work with your physician to determine what is best with you.

COVID.Aside from lingering issues like inability to smell properly, C*V1D can cause hair loss. A Lancet STUDY showed that 22% of hospitalized patients reported hair loss 6 months later. Its from increased hair shedding. We know that tremendous stress on the body leads to hair loss, and the hair loss occurs months later. So it may be a combination of stress from hospitalization, as well as something that the virus itself does to the body. Either way, this is a consideration for many people today who have had the respiratory illness, and now suddenly have wads of hair falling out. I would think it is temporary.

The fixfor illness:The fix here would be time and probiotics. Time will allow your body to reduce all those stress chemicals that you had during illness. The probiotics havethe ability to counteract hair loss by supporting your bodyin a unique way more specifically they can help manage new hair growth and support the health of your hair follicles which enable faster hair growth.

Certainly, other factors may be involved like antibody formation to ones own hair follicles, but that has yet to be teased out. It may very well also cause telogen effluvium which I will discuss next.

Antibiotics and Antifungals.Many people today are treating themselves for mold illness or other infections such as Lyme disease, H. pylori, SIBO, or even acne. The medications that kill organisms are well known to cause hair loss, and this begins about 2 to 4 months into drug therapy. Its often overlooked by doctors who have one goal in mind, that is to cure your infection.

But the hair loss can be profound and frightening to the patient, so Im listing this category of medications so you understand what is happening and can take action. Itraconazole therapy is widely known to cause hair loss, and the first case study I could find was from 1986. Its no secret, but the importance of this medication and similar ones for serious illness cannot be dismissed, nor can they be discontinued if they are for a life-threatening systemic infection.

The antibiotics and antifungals can interfere with your normal cycle of hair growth. The term for this is called Telogen effluvium which causes the hair roots to be forced into a resting state. Telogen hair shedding is a condition can be acute or chronic and with medications, I would guess its chronic until discontinuation of the offending agent. After that it may take 6 months to a year to regrow.

The fix for antibiotics and anti-fungals:Probiotics can help for the same reason I explained earlier in this article. Probiotics have a counter effect to the intestinal damage done by the antibiotics. Looking into natural remedies may also be useful to some of you if the medications are too harsh. For example, Oil of Oregano and Enteric Coated Peppermint Oil capsules, Andrographis, and even Berberine are useful for some situations like SIBO, and Lyme, systemic mycosis and more! There are hundreds of choices when it comes to natural antimicrobials. If you can talk to your doctor about using more simple remedies, then perhaps the hair loss will not be so profound.

Collagen Loss.As we age, our ability to produce collagen diminishes. Because collagen protects the skin, and the layer of skin that holds the hair roots, it may help indirectly with age-related hair loss. To be clear, collagen is not really in the hair, it simply supports the hair follicle. Collagen production goes down with age, so its one piece of the puzzle.

The fix for collagen loss:Consider collagen peptides which go on to form collagen in the body. It can support healthy beautiful skin, as well as hair since the collagen peptides help build hair proteins and strengthen skin around your hair roots.

Reduced Parathyroid Hormone.The condition is termed Hypoparathyroidism. This has nothing to do with the thyroid gland, it is another set of glands that reside behind your thyroid gland, and there are four of them. The parathyroid glands regulate calcium and produce parathyroid hormone or PTH.

Symptoms of low parathyroid hormone include brittle nails, patchy hair loss, thinning eyebrows, anxiety and sometimes muscle weakness, fatigue and headaches. Most doctors do not test for the condition, but its quite common. So is the opposite condition called Hyperparathyroidism where the parathyroid glands produce too much parathyroid hormone (PTH).

If you have low PTH, you will experience hair loss and you can go for years without them figuring this out!

The fix for low PTH:Test yourself by self-ordering your own blood test, or asking your doctor to test forPTH hormone, along with vitamin D, serum calcium and ionized calcium.All four of these tests is critical. You will go from there when you get your results because the treatment for low PTH is different than the treatment for high PTH.

Oftentimes, the treatment for low PTH is simple, and nutrients are used, or PTH hormone is given to restore declining levels. But either way, at least you will know if your hair loss is being driven by a problem of the parathyroid glands. There is more information in thisPAPER

for doctors reading this today who want to understand the mechanisms behind the PTH-driven hair loss.

A PTH blood test, along with the others listed above is a very simple, affordable way to evaluate any person experiencing chronic fatigue and hair loss! If left untreated, the PTH imbalance can lead to heart problems such as Left Ventricular Hypertrophy and more. The best site for information on the parathyroid gland isparathyroid.com.Ive also written an article about calcium and PTH which may be useful and it is availableHERE.

Autoimmune Process.Many people suffer with autoimmune disease and do not even know it. Thats because the symptoms get treated one by one, with one medication at a time.You have joint pain, you get celecoxib.You have fatigue, or night sweats, youll be given an antidepressant or estrogen drug.You have neuropathy, you get gabapentin.You have a few white spots on your skin, so now you get clobetasol or betamethasone.You get a low thyroid test, so you are put on levothyroxine.You have dry eyes or dry cough, youll be given a few more drugs!

All of these symptoms could actually be autoimmune driven. In the same respective order, it would look like this:

You have joint pain, it might be Rheumatoid Arthritis.You have neuropathy, it could be Small Fiber Neuropathy, Multiple Sclerosis or Autoimmune NeuropathyYou have fatigue, or night sweats, it may be Sarcoidosis.You have a few white spots on your skin, you could have Vitiligo.You have dry eyes or dry cough, you may have Sjgrensdisease.You get a bad thyroid test, you may haveHashimotos thyroiditisorGraves disease.

My point is to make you wonder if youve been diagnosed properly, because if you have any one of these autoimmune disorders, you could also have antibodies against your own hair follicles. Hair loss is very common with all of the conditions above. Autoimmune illness is a very common, but overlooked cause for hair loss. Another one that comes to mind that I didnt list above is Celiac disease. Because the gut cannot absorb all the nutrients like normal, a deficiency may occur, which then affects hair growth. Many laboratories today test for autoimmune illness.

The fix for autoimmune process:First of all, make sure you are diagnosed properly. If you think your hair loss is being driven by an autoimmune process, you can look into new, appropriate methods of treatment. What I mean specifically, is if you are only being treated for dry eyes with a fish oil supplement, but you find out that you actually have Sjgrens, then you can get proper treatment for the Sjgrens and that in and of itself may slow down the hair loss. Improper treatment of an autoimmune process only allows the self-attack to continue. So one fix is getting adequate, proper treatment for your specific illness and your physician will help you do that. The other fix for an autoimmune illness is to improve your diet. Nothing makes the body weaker than eating junk food, and exposing yourself to more free radicals which increase the inflammatory cytokines. So a clean, healthy, well-balanced diet is critical. Gluten and casein are two common proteins which exacerbate autoimmunity.

In closing, there are many common, but overlooked causes for hair loss. I encourage you to do more searching into the possible reasons behind your hair loss, and not to give up. As always, I would urge you to consider taking nutrients that are known to support hair growth and eating a healthy diet that excludes unhealthy oils and refined or manufactured foods. I would also encourage you to avoid excessive or harsh hair treatments which can ultimately contribute to hair loss.

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Common But Overlooked Causes for Hair Loss - The Cherokee Scout

Whether you're still coming to terms with that earlier pre-commute wake-up call or being kept awake by the little ones on the nightly, it's likely you're feeling (and seeing) the results of disrupted sleep. According to a study from the University of Southampton, the number of people experiencing insomnia rose from one in six to one in four during the height of the pandemic and the majority are experiencing more of the same.

'The last 18 months have been turbulent, and we need to prioritise sleep more than ever', says Dr Anna Persaud, CEO of This Works. 'It is essential good health, well-being and quality of life.'

Nights spent tossing and turning have an impact on our energy levels and yes, our skin too.

Skin cells have their own schedule. Sleep paves the way for their 'repair and renew' phase, that's when stem cells work to replace old cells with bright, shiny, new fully-functioning ones. The less sleep we get, the less efficient this process is. Enter dull, lacklustre skin. So, how to combat it?

According to skincare and laser specialist Debbie Thomas, gentle exfoliation can mimic the glow you get from a great night's sleep. 'To brighten up the skin first of all address your exfoliation. Gentle and regular is best, I always recommend a liquid exfoliator over a scrub, think acids or enzymes.'

Work vitamin C into your morning skincare routine too. 'Vitamin C is known for its brightening qualities,' explains Thomas, 'and with consistent use it also helps boost collagen levels too.' Never underestimate a two-pronged approach.

Who doesn't wake up with a slightly puffy face in the morning? Puffiness comes from fluid retention and fluid retention can be eased with a gentle lymphatic drainage massage. 'De-puffing your face takes a little gentle arm work', says Thomas. 'While washing your face with a slippery cleanser, use the heel of your hand to firmly massage up and out in sweeping movements to push the fluid build-up towards your ears and the lymph nodes. The idea is to push up to lift then sweep out to drain. Just make sure that your skin is a little slippery so that you aren't tugging at it.'

'For puffy eyes specifically, reach for something cold,' advises Thomas. 'Holding something cold against your eye area helps to tone down inflammation and puffiness. If you don't own a cryo-massage tool then grab an ice cube with some tissue, let it warm enough to be slippery on your skin then sweep it around your eyes and over your skin for 1-2 minutes.'

It goes without saying, but routine is key says This Works sleep expert Dr Anna Persaud. 'On a practical level establishing and maintaining a nightly wind down or sleep routine helps to reset and rebalance our minds. Try dimming lights, limiting brain stimulation - for example turning off Netflix an hour earlier and disconnecting from our devices - can help to signal to our brain that it is time to sleep.'

And from a beauty perspective? Never knock the instant results of a decent under-eye concealer.

This new overnight mask is infused with kombucha to help combat irritation and redness, and niacinamide for super soft, supple skin. Simply pop on overnight and let it get to work whilst you sleep, leaving skin refreshed, energised and glowy with minimal work. A time saving treasure.

A one stop shop for refreshed and rejuvenated skin, the Essential Skin Grade treatment combines the necessary services for your skin concerns as recommended by consultation. Think mild peels, extractions, microdermabrasion, Byonik pulse triggered cold laser, photodynamic red and blue light therapy, lymphatic drainage, radiofrequency, and ultrasound product infusion, as well as an assortment of serums and masks

"Our collection of pillow sprays all contain a clinically proven Sleep Superblend to you fall asleep faster. A natural, aromatherapeutic fragrance with 100% natural essential oils including French Lavender, wild Camomile and Vetivert. The Sleep Plus, Love Sleep and Deep Sleep Pillow Sprays calm both the mind and body and target various sleep issues. Independent consumer studies found that after using the product, 97% reported less broken sleep and 89% said they fell asleep more quickly than usual. As a result of using Deep Sleep Pillow Spray, 98% felt more relaxed in the morning and 97% felt less tired the day after using. We've sold over 8 million pillow sprays thanks to ongoing scientific research and continuous product innovation so it's fair to say they really work." Dr Anna Persaud, CEO, This Works and VP Skincare & Topicals, Canopy Growth

Angela Caglia's ultra-luxurious Self Love Rose Quartz Eye Mask is garnering a cult following for its calming and soothing properties. If you're drawn to the energy in crystals, real rose quartz is woven together to create a pampering eye mask to release tension and focus the mind. Sign us up.

"You don't need us to tell you that sleeping is a fundamental part of a healthy lifestyle", says Becky O'Neill, Global Brand Manager of Sanctuary Spa. "It improves concentration levels, mood and ability to cope with stress. Getting a good night's rest also lowers the levels of cortisol in the body, promoting a healthy and stress-free mindset". So soak away the days stress with Sanctuary Spa's wellness bath salts. The rest of the range includes a CBD calming oil, de-stress balm and pillow spray to help you properly unwind from bath to bed.

To touch up dark circles on the go, this full coverage but easily blendable concealer has a smooth, buttery formula that blends seamlessly into skin for a brightening lift. The best part? It doesn't dry out and crack, so this second skin will last as long as your day does.

This lightweight but potent serum packs a punch to give fatigued skin a dose of Vitamin C for a brighter complexion, and perceptibly plumper and more even skin. Use before moisturiser for a shot of extra hydration.

According to Slip, 'by the time we are 60 we will have slept for an average of 20 years' so better make that time count. This pure silk eye mask (and accompanying range of pillowcases) are anti aging, anti sleep crease, anti bed head and can help to reduce friction and irritation on delicate facial skin. Perfect for blocking out the early morning light and getting you to sleep through to your alarm.

Ease tense and aching joints with this concentrated CBD balm that is a non-greasy and easily absorbed formula, to massage into localised areas and melt away stress.

Aromatherapy is great for unwinding, and this calming and tranquil scented candle has notes of Lavender and Ylang Ylang. to help you take a moment to ground yourself and reset.

READ MORE: The Best Body Scrubs To Soften Dry Winter Skin, Fast

READ MORE: November 2021 Beauty Edit: The Best New Beauty Buys Out This Month

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How To Look Less Tired According To Experts | Grazia - Grazia

Every person, every mouse, every dog, has one unmistakable sign of aging: hair loss. But why does that happen?

Rui Yi, a professor of pathology at Northwestern University, set out to answer the question.

A generally accepted hypothesis about stem cells says they replenish tissues and organs, including hair, but they will eventually be exhausted and then die in place. This process is seen as an integral part of aging.

Instead Dr. Yi and his colleagues made a surprising discovery that, at least in the hair of aging animals, stem cells escape from the structures that house them.

Its a new way of thinking about aging, said Dr. Cheng-Ming Chuong, a skin cell researcher and professor of pathology at the University of Southern California, who was not involved in Dr. Yis study, which was published on Monday in the journal Nature Aging.

The study also identifies two genes involved in the aging of hair, opening up new possibilities for stopping the process by preventing stem cells from escaping.

Charles K.F. Chan, a stem cell researcher at Stanford University, called the paper very important, noting that in science, everything about aging seems so complicated we dont know where to start. By showing a pathway and a mechanism for explaining aging hair, Dr. Yi and colleagues may have provided a toehold.

Stem cells play a crucial role in the growth of hair in mice and in humans. Hair follicles, the tunnel-shaped miniature organs from which hairs grow, go through cyclical periods of growth in which a population of stem cells living in a specialized region called the bulge divide and become rapidly growing hair cells.

Sarah Millar, director of the Black Family Stem Cell Institute at the Icahn School of Medicine at Mount Sinai, who was not involved in Dr. Yis paper, explained that those cells give rise to the hair shaft and its sheath. Then, after a period of time, which is short for human body hair and much longer for hair on a persons head, the follicle becomes inactive and its lower part degenerates. The hair shaft stops growing and is shed, only to be replaced by a new strand of hair as the cycle repeats.

But while the rest of the follicle dies, a collection of stem cells remains in the bulge, ready to start turning into hair cells to grow a new strand of hair.

Dr. Yi, like most scientists, had assumed that with age the stem cells died in a process known as stem cell exhaustion. He expected that the death of a hair follicles stem cells meant that the hair would turn white and, when enough stem cells were lost, the strand of hair would die. But this hypothesis had not been fully tested.

Together with a graduate student, Chi Zhang, Dr. Yi decided that to understand the aging process in hair, he needed to watch individual strands of hair as they grew and aged.

Ordinarily, researchers who study aging take chunks of tissue from animals of different ages and examine the changes. There are two drawbacks to this approach, Dr. Yi said. First, the tissue is already dead. And it is not clear what led to the changes that are observed or what will come after them.

He decided his team would use a different method. They watched the growth of individual hair follicles in the ears of mice using a long wavelength laser that can penetrate deep into tissue. They labeled hair follicles with a green fluorescent protein, anesthetized the animals so they did not move, put their ear under the microscope and went back again and again to watch what was happening to the same hair follicle.

What they saw was a surprise: When the animals started to grow old and gray and lose their hair, their stem cells started to escape their little homes in the bulge. The cells changed their shapes from round to amoeba-like and squeezed out of tiny holes in the follicle. Then they recovered their normal shapes and darted away.

Sometimes, the escaping stem cells leapt long distances, in cellular terms, from the niche where they lived.

If I did not see it for myself I would not have believed it, Dr. Yi said. Its almost crazy in my mind.

The stem cells then vanished, perhaps consumed by the immune system.

Dr. Chan compared an animal's body to a car. If you run it long enough and dont replace parts, things wear out, he said. In the body, stem cells are like a mechanic, providing replacement parts, and in some organs like hair, blood and bone, the replacement is continual.

But with hair, it now looks as if the mechanic the stem cells simply walks off the job one day.

But why? Dr. Yi and his colleagues next step was to ask if genes are controlling the process. They discovered two FOXC1 and NFATC1 that were less active in older hair follicle cells. Their role was to imprison stem cells in the bulge. So the researchers bred mice that lacked those genes to see if they were the master controllers.

By the time the mice were 4 to 5 months old, they started losing hair. By age 16 months, when the animals were middle-aged, they looked ancient: They had lost a lot of hair and the sparse strands remaining were gray.

Now the researchers want to save the hair stem cells in aging mice.

This story of the discovery of a completely unexpected natural process makes Dr. Chuong wonder what remains to be learned about living creatures.

Nature has endless surprises waiting for us, he said. You can see fantastic things.

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Losing Your Hair? You Might Blame the Great Stem Cell Escape. - The New York Times

It is too late for conservation efforts to save the northern white rhinoceros, but with recent scientific advancements there may still be hope to bring back this beloved species. In a recently published paper, scientist Marisa Korody and her colleagues at San Diego Zoo Global (USA) and at the Department of Molecular Medicine at Scripps Research (USA) describe their exciting progress on using stem cells to revive the northern white rhino.

The northern white rhino is functionally extinct, meaning there are not enough of these rhinos left to save the species. In fact there are only two northern white rhinos left: a mother and a daughter. But for decades, scientists have preserved cell samples from 15 northern white rhinos containing enough genetic material to potentially bring this species back from the brink. These preserved samples hold fibroblast cells the type of skin cells that secrete collagen from white rhinos. With these scientists newly developed methods, fibroblast cells can be converted into something much more valuable: induced pluripotent stem cells. These stem cells can differentiate into any cell type in the body including heart cells, muscle cells, and reproductive cells.

In theory, by converting fibroblast cells into reproductive cells, scientists could create genetically unique rhino embryos. Alongside other assisted reproduction technologies, scientists could implant a new embryo into a closely-related southern white rhino, where the baby northern white rhino could develop as an otherwise normal pregnancy. By completing this process multiple times, scientists may be able to establish a stable population of northern white rhinos.

In 2011, this research team generated induced pluripotent stem cells from the samples of another endangered species, but unfortunately since this process was found to harm the recipient genomes, this method was largely unsuccessful. Despite this setback, in 2015 the authors met with colleagues worldwide to consider ways to save the northern white rhino, and they concluded that methods involving induced pluripotent stem cells may still be the most promising solution. Over the following years, the scientists worked to improve their methods, and these improvements are documented in their recent paper. These experiments represent the first step in a long-term plan to bring the northern white rhino back through assisted reproduction techniques.

Right from the start, the scientists faced a whole host of challenges. Through trial and error they modified the growth medium for the cells, optimizing it for rhinoceros cells. With their improved growth medium, scientists successfully generated induced pluripotent stem cell lines from 11 rhinoceros individuals. This has never been done before and represents a huge stride forward in the path to recovering this species.

Before trying to make their first rhino, the scientists needed to stress these induced pluripotent stem cells and sequence their genomes to determine if the cell quality is good enough to potentially produce new, viable rhinos. They maintained colonies of these cells in long-term cultures and exposed these colonies to different conditions to give insight into how resilient these cells could be. These tests demonstrated that long-term culture did not affect the potential for these cells to differentiate into cardiac lineage cells, confirming that these cells are stable long-term. The researchers also confirmed that these pluripotent cells could potentially produce gametes, the egg and sperm cells that are used for sexual reproduction. These advancements indicate that with these newly developed protocols, induced pluripotent stem cells are a promising tool that could someday help recover the northern white rhino.

Although this study includes some exciting results, there is still much work to do. For example, scientists must now sequence the genomes of the northern and southern white rhino so other researchers can analyze the stem cells ability to stay the same over time. Despite the work that still needs to be done, these promising advancements could someday help the northern white rhino population recover. This method may also work for saving other endangered or extinct species, as long as the genetic material needed is available. Long-term, these scientists plan to continue a series of experiments that could ultimately bring this beloved rhino, and potentially other endangered species, back from the brink of extinction.

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Stem cells may be the key to saving white rhinos from extinction - Sciworthy

As a beauty writer and longtime skincare fanatic, Ive subscribed to various multi-step routines. Fast forward to having a baby and the general day-to-day life upheaval that comes along with it, and my definition of a worthwhile personal beauty regimen has changed a bit. While I still enjoy trying new products and learning about innovations in the beauty space, I find myself with less time (and patience) for the more laborious treatments and layering routines, and more interest in noticeable efficacy and multitasking capabilities.

The most effective skincare products and tools are great for paring down your routineand also ... [+] saving you some precious minutes in your day.

And whether youre a busy mom or simply short on me time these days (who isnt?), there are a myriad of tried-and-true products that get the job done without requiring a ton of effort on your part. From Herauxs next-level anti-inflammaging serum to NuFaces skin-smoothing device, these standout skincare products and tools are ideal for a results-driven regimen thats effective enough to knock a few steps off your routineand save you some precious minutes in your day.

Since its launch seven years ago, this antioxidant-rich hydrating facial oil has remained a cult favorite for anyone who wants an instant glow, with the added benefit of skin soothing, balancing and repair. Infused with 22 active botanical and essential oils, the lightweight yet potent treatment can help with everything from acne to sun damage. And when applied using founder April Gargiulos signature push-press technique, it feels like a simple yet luxurious way to start and end the day.

Like the brands Trinity device, the NuFace Fix uses microcurrent technology at a gentler level to help reduce the look of fine lines and wrinkles on the more delicate areas of the face: on the forehead, between brows and around the eyes and lips (filler-free plumping, anyone?). Its sleek, compact shape combined with ease of use makes it a no-brainer for skin smoothing results in a matter of minutes. Plus, it holds an ample 120-minute charge, which amounts to a couple months worth of use before needing to plug it ini.e. no fumbling with cords or a hefty device on a regular basis.

The latest product in Kate McLeods sustainably packaged, handcrafted self care collection and the first to focus on skincare, the Face Stone is essentially a waterless moisturizer that melts on contact with skin. A rich blend of nourishing and antioxidant ingredients like blue tansy, kokum butter and plum kernal borage helps even and soothe stressed skinsomething we could all use these days. An added bonus? Its solid form and shape makes it a natural massaging tool, making it ideal for a morning pick-me-up or the start of an evening wind-down ritual.

While it covers your mineral-based broad spectrum sunscreen needs, this multitasker does much more than that. The unique product uses the U Beautys proprietary Sun-Siren Capsule Technology to help reduce hyperpigmentation, discoloration and dark spots (whether from pregnancy melasma or suntanning sins of the past) while also shielding against UVA, UVB, infrared and blue light exposure. A little goes a long way with this rich balm-cream formula, and its hydrating enough to double as a moisturizer or primer by day and also great as an overnight spot treatment.

An excellent (and cleaner) dupe for Biologique Recherches oft-elusive Lotion P50, this Moon Juice exfoliator is a skin savior in its own right. The liquid formula includes glycolic, lactic and salicylic acids for gentle, pore-minimizing exfoliation paired with niacinamide and adaptogenic reishi to help boost the skins natural barrier. And besides looking pretty, the packaging is completely recyclable, from the sculptural cap and glass bottle to the outer carton.

January Labs is a clean beauty favorite for its science-backed, results-driven products that have long been favored by top aestheticians. Even those with more sensitive (or dry) skin can use this retinol serum without dealing with typical downsides (like redness, drying or peeling) thanks to its use of Retistar, a .5% retinol thats super effective yet non-irritating.

This at-home peel is as easy as can be, requiring a single once-over with the pre-soaked pad to revive dull skin. The duo of glycolic and salicylic acids provide skin-smoothing exfoliation while ingredients like chamomile and bilberry extract calm, soothe and help even skin tone. Pro tip: Use up excess product on any dry, flakey patches on arms and legs.

Created by stem cell biologists at the University of Southern California, this innovative serum features an anti-inflammaging HX-1 molecule thats combined with tried-and-tested ingredients like vitamin C, hyaluronic acid, peptides and red maple bark. The result? A silky, lightweight formula thats both rejuvenating (designed to help reduce the effects of stress and aging factors on skin) and preventative (strengthening stem cells on a molecular level).

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The Best Skincare Treatments For Time-Crunched Moms (Or Anyone Else Who Only Has Five Minutes To Spare) - Forbes

A recent article in the journal Nature credits Stanford physician-neuroscientist Sergiu Pasca, MD, with blazing a trail toward a more profound understanding of early brain development, and of what can go wrong in the process, using a cell-based research innovation he named "assembloids."

In 2015, Pasca and his colleagues published a paper in Nature Methods describing a fascinating feat: His tinkering with induced pluripotent stem cells, or iPS cells -- former skin cells transformed so that they've acquired an almost magical capacity to generate all the tissues in the body -- had borne a three-dimensional product. From these "magic" iPS cells grew a complex conglomerate of cells capable of modeling specific organs.

Pasca's particular interest was in the brain, and in the experiments detailed in the study, his lab had caused human iPS cells to multiply and differentiate into small spherical clusters of brain tissue suspended in laboratory glassware.

These clusters recapitulated the architecture and physiology of the human cerebral cortex -- the outermost layer of brain tissue, critical to perception, cognition and action. Pasca named these clusters, which grew to several millimeters in diameter and contained millions of cells, "cortical spheroids." Today, researchers around the world are using similar methodology to create models, broadly known as "organoids," to study other parts of the human body.

Two years later, in a study published in Nature, Pasca upped the ante by, first, generating a second kind of neural spheroid -- this time, representative of a deeper part of the developing forebrain called the subpallium -- and, second, by growing this kind of spheroid in conjunction with cortical spheroids, in the same dish.

To the researchers' amazement, spheroids of both types fused together, with nerve cells from subpallial spheroids migrating and poking extensions into the cortical spheroids and establishing working connections with nerve cells of a different type in the latter spheroids, just as occurs in fetal development.

"It's amazing that these cells already self-organize and know what they need to do," Pasca marveled in "Brain Balls," an article I wrote for our magazine, Stanford Medicine, a few years ago.

Pasca sensibly dubbed the two-fused-spheroid combos "assembloids," the Nature recap notes.

But why stop at two? Pasca has since created three-element assembloids composed of spheroids representative of cerebral cortex, spinal cord and skeletal muscle in order to model the circuitry of voluntary movement. He's also shown that stimulating the "cerebral cortex" spheroid can result in contraction of the "muscle" spheroid. (This accomplishment was published in Cell in late 2020.) He has explored other assembloid combinations, as well, such as the fusing of cortical spheroids with spheroids representing the striatum, a brain structure implicated in regulating our movements and responses to rewarding and aversive stimuli.

Because each spheroid begins with skin cells, they can be grown on a personalized basis -- and can therefore be extracted from patients with neurological disorders known or suspected to spring from early developmental aberrations (such as autism or schizophrenia). The cells can then be used to create models to probe these disorders' molecular, cellular and circuit-based deviations from the pathways of normal brain development, allowing scientists to study the brain in way they could never do with a living patient.

From the Nature article:

Assembloids are now at the leading edge of stem-cell research. Scientists are using them to investigate early events in organ development as tools for studying not only psychiatric disorders, but other types of disease as well.

An assembloid is by no means a complete, working brain. But, the article notes, "Pasca stands by the aphorism that all models are wrong, and some are useful. 'There's been important progress in the field in a short period of time,' he says."

Photo courtesy of the Pasca laboratory

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Stanford neuroscientist's 'assembloids' pave the way for innovative brain research - Scope

Fall is here, and now is the perfect time to upgrade your beauty routine for the cooler temperatures. Here are a few of our favorite products:

Parfums de Marly

The famed perfume house founded by Julien Sprecher will launch sensual Oriana on September 12th. Packaged in a hot pink bottle, the airy and dreamy fragrance is captivating withnotes of orange blossom, marshmallow, and Chantilly cream. Available on parfums-de-marly.com and Saks Fifth Avenue. $320.

ILONA

This innovative skincare brand continuously seeks out innovative ingredients and technologies from around the world and incorporates them into premium high-performance formulas like the BEYOND C Corrective Serum. This reincarnating serum is housed in a beautiful dual vessel package. One side is black, the other gold with each containing corrective technologies that reach maximum potency at the moment of unity.

The black side contains a novel probiotic and micronized niacin that fortifies skin defenses, intensifies cellular activity, quells inflammation, and amends blotchiness. The gold vessel contains a patented, hyper-potent, permeable form of vitamin C that helps brighten, fade age spots, even skin tone, and protect against oxidation. $132.

Heraux

This innovative product was created by Heraux Co-Founder Dr. Ben Van Handel, a Stem Cell Biologist at the University of Southern California and leading inflammaging researcher. Dr. Handel notes that Retinols are anti-inflammatory at the molecular level, acting as antioxidants and blocking hyperactivation of the immune system. HX-1, the proprietary ingredient in HerauxsMolecular Anti-Inflammaging Serum, acts to shield skin stem cells from pro-inflammaging stressors and concurrently supports the youthful function of stem cells. The regenerative program enabled by HX-1 promotes the secretion of collagen and elastin as well as improved skin barrier function.

Kimberly Fisher is a Pursuitist contributor. As a freelance writer and on-camera host, Kimberly has traveled the world and has published over 400 articles in over 44 publications including Sherman's Travel, Huffington Post, Just Luxe, Luxury Lifestyles UK, eHow, Examiner, Food Wine Travel Magazine, Luxe Beat, NiteGuide, Ocean View, and USA Today. Disclosure: Kimberly is employed by Remy Cointreau Americas.

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3 of the Best Fall Beauty Buys - Pursuitist