Archive for the ‘Skin Stem Cells’ Category
Tried and Tested: Can Bio Regenerative Skincare really reverse ageing? LLM tried it out – Luxury Lifestyle Magazine
Words by Melissa Harvey
I might still be 25 in my head, but theres no avoiding the fact Im two decades older when I look in the mirror. In the last couple of years, things have definitely gone south (literally). The fine lines around my eyes are starting to look more like crevices, the wrinkles in my forehead dont soften however well rested I am and my skin seems permanently tired and dull. Though Ive always steered clear of Botox, Id started to wonder if I should bite the bullet and give it a go.
Then I heard about the space age-sounding epigenetic skincare. Epigenetics is the study of the way genes are controlled in the body including how lifestyle and environment can affect the way genes work. Unlike genetic changes, epigenetic changes can be stopped and even reversed and are thought to be responsible for 75% of the ageing process. Needless to say, beauty companies have been researching epigenetics for years in the hope of finally finding the ultimate anti-ageing holy grail.
Based in the US, ABG Lab has now developed the worlds first mesotherapy treatments that use this science to turn the clock back on ageing skin. Its launched four treatments at The Harley Street Skin Clinic in London which target mature skin cells with a range of intradermal injectables.
One (MesoEye C71) is designed to target dark circles and eye bags, another (MesoSculpt C71) breaks down fat cells to sculpt and define, smooth cellulite and tighten skin. A third (Meso-Xanthin F199) is best for polluted, damaged skin and photo-ageing and is aimed at those in their 20s and 30s.
Finally, Meso-Wharton P199 is best for those in their 40s and 50s like me. It uses ABG Labs Whartons Jelly Peptide containing synthetic embryonic peptides to target stem cells deep in the skin to keep them functioning well for as long as possible. Its even been claimed that it can reinvigorate the stem cell activity of someone in their 40s to levels of a 25-year-old which had me racing to book in with Dr Aamer Khan, founder of The Harley Street Skin Clinic.
Meso-Wharton speaks to the stem cells and regenerative cells and gets them to behave like when you were younger, he tells me. As we get into our 50s, were reaching the point where very few of our cells are producing collagen. It stimulates the stem cells to produce more collagen so you get younger looking skin.
The bad news is its likely not for you if you hate needles. Four to six treatments are recommended, around a week or two apart, and each treatment involves wait for it around 200 quick intradermal injections all over the face. Though Im told the needle is much smaller than the one used for Botox, its still a little painful even though a numbing cream is applied first. However, I did find each subsequent treatment hurt less, perhaps because I knew what to expect plus its all over in less than ten minutes.
Downtime takes a lot longer. Though some people look normal within 24 hours, it took my skin around six days to settle after each treatment. For the first couple of days, my entire face was covered with small bumps like mosquito bites and I had some bruising after that, though this could be covered with makeup. This would be significantly less obvious in someone without my pale skin however.
About a month after my final treatment, I start to notice small changes. I still look exactly like myself theres no ironed forehead effect but just a bit better and more refreshed. The shadows under my eyes are less obvious and my wrinkles are softer and shallower. My skin looks and feels more hydrated, particularly first thing in the morning. Suddenly, people start unexpectedly telling me I look well (aka less like an exhausted wreck than usual).
Amazingly, epigenetic skincare really has rewound the clock on my rapidly ageing face, although a top-up treatment is needed every three to six months to maintain the radiant, youthful and pleasingly natural effect.
Meso-Wharton P199 is available at The Harley Street Skin Clinic from 450 per session (a course of three to six is recommended). Visit harleystreetskinclinic.com or call 020 7436 4441.
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Tried and Tested: Can Bio Regenerative Skincare really reverse ageing? LLM tried it out - Luxury Lifestyle Magazine
Role of umbilical cord mesenchymal stromal cells in skin rejuvenation | npj Regenerative Medicine – Nature.com
The skin is the largest organ of the human body and has a surface area of 1.52m2, covering the surface of the human body. It is in direct contact with the external environment and protects us from environmental factors1. The skin consists of three parts: the epidermis, dermis, and subcutaneous tissue, which jointly protect internal organs and perform different biological functions. The epidermis is located in the outermost layer of the body and plays a major defensive role2. The dermis is mainly responsible for the synthesis, deposition, and remodeling of the dermal extracellular matrix (ECM), which supports the structural integrity of the skin3,4. Dermal fibroblasts are the main cells in the dermis and synthesize and secrete collagen, elastin and proteoglycan to give strength and elasticity to the skin5. Subcutaneous tissue is located in the deepest layer of the skin and is rich in fat cells and blood vessels; it can support, warm, and provide nutrition for the dermis6. Skin appearance is the main factor used to evaluate age and health status. With the emergence of aging complications and the improvement in quality of life, people are highly motivated to maintain a youthful appearance. Therefore, how to prevent and delay skin aging is important for the general public, thereby stimulating the in-depth study of antiaging by researchers.
Under aging and the decline in the structure and function of skin tissue stimulated by external factors, many functional cells in skin tissue undergo senescence and apoptosis, while new cells lack the ability to self-renew. To resolve the insufficient self-renewal ability of cells in skin tissue, some researchers have proposed that skin cells can be replenished by activating stem cells in skin tissue. However, long-term activation and mobilization will lead to the depletion of stem cells in the body and the complete loss of the ability of cells in the skin to self-renew7. It has been reported that MSCs transplantation can improve skin conditions to some extent8. Therefore, exogenous supplementation of MSCs may be an effective method. The term MSCs originated from the isolation of the bone marrow in 1988 Marrow Stromal Stem Cells9, and named Mesenchymal Stem cells by A.I. Caplan in 199110, ISCT changed to Mesenchymal Stromal Cells in 200611, A.I. Caplan himself applied to ISCT in 2017 to change Mesenchymal Stem Cells to Medicinal Signaling Cells12, ISCT stated in 2019 that it was not in favor of dropping the term mesenchymal and recommended that the acronym MSC continue to be used, but with a note on the functional definition13. The naming of MSCs is still controversial, but with further research, increasing evidence suggests that the therapeutic role of MSCs is largely attributed to their paracrine function.
In this paper, we focus on the study of UC-MSCs in skin aging. On the one hand, umbilical cords are medical waste, and as a result, using them avoids the limitation of source and ethical issues14,15,16,17,18. On the other hand, the efficacy of MSCs decreases with the increase of their number of divisions, because cell division shortens telomeres and leads to cell senescence19,20. An earlier 2012 follow-up study of patients with the acute graft-versa-host disease (GVHD) treated with MSCs showed a significant increase in one-year survival (75% vs 21%) in MSCs receiving early passage (from generation 12) compared to MSC patients receiving late passage (from generation 34)21. In addition, the regenerative potential of MSCs also decreases with the age of donors22. Therefore, the UC-MSCs are isolated from neonatal tissues and seem to be younger than other sources of MSCs23. Their high activity, increased pluripotency, low immunogenicity, and suitable paracrine effects have been indicated24,25. Previous studies have shown that UC-MSCs can be induced to differentiate into various types of functional cells in vitro, such as keratinocytes and dermal fibroblasts, which provides a variety of potential strategies for the treatment of skin diseases and the development of medical beauty products26. It also made many researchers once believe that the efficacy of MSCs is mainly played by their differentiation into specific functional cells, so that the efficacy of MSCs is infinitely amplified, resulting in over-marketing of Stemcells on the market. However, subsequent studies have seen little evidence that MSCs can differentiate into specific functional cells in vivo, so it is believed that the paracrine role of MSCs is the main way to exert their therapeutic effect. This may also be the reason why A.I. Caplan applied to ISCT in 2017 to change Mesenchymal Stem Cells to Medicinal Signaling Cells.
Human skin is a dynamic and complex organ that is composed of different cell types and functional regions. Like other organs, the skin ages and is characterized by structural destruction and gradual loss of function. Aging caused by genetic, metabolic, and other internal factors is called intrinsic aging, while aging caused by environmental factors such as ultraviolet rays, nutrition, air pollution, cigarettes, temperature, and pressure is called extrinsic aging27.
For naturally aging skin, histological changes mainly occur in the basal layer and dermis. The basal layer of the skin is located in the deepest layer of the epidermis and participates in the repair and regeneration of the skin. Studies have shown that the proliferation of basal cells of the skin, such as keratinocytes and melanocytes, decreases with age, resulting in a thinning of the skin epidermis28,29. Moreover, the fibrous ECM components such as elastin, fibrin, and collagen in the dermis degenerate, the skin is dehydrated, elasticity decreases, and wrinkles appear30,31. With age, the repair ability of skin cells decreases, resulting in intrinsic skin aging.
Extrinsic aging is far more serious than endogenous aging; ultraviolet radiation (UVR) has the greatest effect, accounting for 80% of facial skin aging32. In contrast to intrinsic aging, UVR thickens the epidermis and promotes the activation of epidermal melanocytes in exposed skin, resulting in pigmentation33. UVR on the skin leads to senescence and apoptosis of skin cells by directly damaging the deoxyribonucleic Acid (DNA), Ribonucleic Acid (RNA), and protein of skin cells34. Moreover, skin cells produce free radicals and reactive oxygen species (ROS) when subjected to UVR, which causes inflammation and promotes mitochondrial membrane potential (MMP) synthesis, indirectly leading to oxidative damage and ECM degradation of skin cells35,36. Photoaging also accelerates skin aging by superimposing intrinsic aging in chronological order.
The ultimate goal of researchers efforts investigating skin aging is to find ways to slow down the rate of aging and improve quality of life by regulating the mechanisms of skin aging. At present, it has been reported that plant extracts37, antioxidants38, growth factors, and cytokines39, as well as MSCs40, can alleviate skin aging41. Since cell therapy was first proposed by Swiss doctors in 1931, the field has made a breakthrough in the research of human diseases. Skin tissue is composed of a large number of mature functional cells, progenitor cells, and a small number of stem cells. Although adult tissue stem cells are rare, they play a major role in human health. The number of adult stem cells gradually decreases after birth, so supplementation with exogenous MSCs may be an effective way to promote tissue repair and regeneration. Umbilical cord mesenchymal stromal cells (UC-MSCs) have become a more promising therapeutic method because of their powerful paracrine function and the ability to secret various cytokines, growth factors, and exogenes to promote tissue regeneration and inhibit inflammatory response. However, MSCs therapy is still in the research stage, and a large amount of experimental data is needed to accelerate its clinical transformation. As of December 2023, over 2000 MSCs clinical trials have been registered at https://clinicaltrials.gov/, including over 400 UC-MSCs clinical trials. Including UC-MSCs for Diabetic Nephropathy, Ulcerative Colitis, Oral Chronic Graft-versus-host Disease, Diabetic Foot, Skin Grafts in Donor Site Wounds, Skin Rejuvenation, Skin Ulcers, and other diseases. This large amount of data reflects the broad interest of the scientific community in the potential therapeutic applications of MSCs. However, among the many clinical trials at different stages, we have collated nine clinical trials of UC-MSCs for skin-related diseases that have been completed and have reported results (Table 1). By combing through these trials, we can gain a clearer understanding of the application of UC-MSCs in clinical practice, as well as the challenges and future directions. Clinical trials are designed to evaluate the efficacy and safety of MSCs in the treatment of various diseases, but clinical trials currently face many difficulties, including developing standardized treatment protocols, monitoring cell survival and function in vivo, and the safety and long-term efficacy of cell therapy. These problems not only increase the complexity of clinical trials, but also limit their wide application in practice. In order to solve the challenges faced by clinical trials, pre-clinical basic research is crucial to provide a reliable theoretical and experimental basis for clinical trials. In the basic research, the establishment of an ideal experimental model is the premise of further research, here we mainly introduce the skin aging research model. Aging research on animal models can simulate the complex environment of human skin aging in combination with in vitro and in vivo aging factors and relatively accurately reflect the characteristics of skin aging, but the accuracy of these results still needs to be verified at the cellular and molecular levels. Cells are the basic unit of the human body; they can be isolated and expanded in vitro under suitable conditions and can reflect the process and law of human aging at the cellular level, so they are widely used as an experimental model in vitro. In order to facilitate the work of subsequent researchers, we have listed in detail the modeling conditions of the currently widely used research models in Table 2, aiming to provide clearer and convenient guidance for future basic research. However, it is worth noting that none of these studies calculated the percentage of actual engrafted cells relative to the total implanted cells, as the actual number of engrafted cells is crucial for assessing therapeutic efficacy. Therefore, future research may need to pay more attention to and carefully consider the calculation of the actual number of engrafted cells to comprehensively understand the effectiveness and mechanisms of MSC therapy.
UC-MSCs are a kind of mesenchymal stromal cell derived from neonatal umbilical cord tissue with abundant material sources, easy amplification, strong plasticity, low immunogenicity, high migration and homing activity, exocrine secretion, and the secretion of a variety of cytokines25. Compared with other MSCs currently used in basic and clinical research, such as adipose mesenchymal stromal cells (ADMSCs), bone marrow mesenchymal stromal cells (BMSCs), dental pulp stromal cells (DPSCs), embryonic stromal cells (ASCs), and neural stem cells (NSCs); UC-MSCs are derived from a wider range of sources; have no ethical or safety challenges; are easier to obtain, expand and store; and can fully meet clinical needs42. UC-MSCs can be induced to differentiate into many types of functional cells in vitro, which is of great significance for the clinical treatment of corresponding diseases. UC-MSCs have been used in the study of cardiovascular disease43, inflammatory bowel disease (IBD)44, chronic obstructive pneumonia (COPD)45, premature ovarian failure (POF)46, skin aging23, and other diseases, and their effectiveness has been proven. This paper mainly summarizes the research progress of UC-MSCs in skin aging. The mechanism of UC-MSCs in the treatment of skin aging can be summarized as promoting injury repair and skin regeneration through anti-inflammatory, antioxidative, and anti-glycosylation mechanisms, as shown in Fig. 1.
The skin shows structural and functional degradation under the action of internal and external factors, and UC-MSCs rejuvenate it by promoting injury repair and regeneration through anti-inflammatory, antioxidative, and anti-glycosylation mechanisms.
Skin tissue integrity, function, and regeneration decrease with age. An increasing number of studies have reported that UC-MSCs can promote the repair of damaged skin through the secretion of cytokines. The homing property of UC-MSCs is the key to their direct participation in the repair of skin injury. Many animal experiments have confirmed that when there is injury in the body, transplanted UC-MSCs can migrate to the injured site, differentiate, and replace injured cells using the chemotaxis of the injured tissue microenvironment47,48,49. However, with the deepening of the research, the view that MSCs differentiate and replace injured cells is no longer supported. After the importation of MSCs into the body, the amount of MSCs in the body is very small (<1%), suggesting that the repair of injuries may primarily involve the paracrine functions of MSCs (Table 3).
To study the role and fate of transfused MSCs, Yins research team explored the fate of type 2 diabetes (T2DM) mice intravenously injected with UC-MSCs compared with that in control mice. This study showed that UC-MSCs first reached the lungs and then migrated through the circulatory system to the spleen and liver. Compared with the control mice, the T2DM mice injected with UC-MSCs showed that the UC-MSCs homed to the islets. UC-MSC infusion not only effectively restored blood glucose homeostasis and reduced insulin resistance in mice but also improved hyperlipidemia and liver function in T2DM mice, suggesting that UC-MSC migration is closely related to tissue injury and can participate in tissue repair50. Zhang et al.51 applied UC-MSCs and UC-MSC-CM locally to the skin wounds of diabetic mice to study their therapeutic effects on wound healing. The results showed that UC-MSCs and UC-MSC-CM significantly increased the overall wound healing rate, improved angiogenesis, and increased the percentage of M2 macrophages in the wound area. Further observation of the local microenvironment of the wound tissue showed that the secreted levels of the anti-inflammatory factors IL-10 and VEGF increased, while the secreted levels of the proinflammatory factors TNF- and IL-6 were inhibited. It is suggested that UC-MSCs can play a role in injury repair by improving angiogenesis and regulating the local tissue microenvironment.
Repair and regeneration are often mistaken for the same concept. In fact, repair mainly refers to the recovery of tissue structure and function. In the context of skin, repair indicates that it may have scars and may not have hair follicles. Regeneration essentially refers to achieving a completely normal state through the proliferation of cells in skin tissue52. UC-MSCs can secrete and synthesize a variety of cytokines that promote cell growth and differentiation to regulate the local microenvironment, including FGF, EGF, VEGF, NGF, PDGF, CSF, and TNF53. These cytokines carry signaling information that can regenerate blood vessels, improve blood circulation, and promote tissue regeneration.
After skin injury model rats were treated with UCBMSC-exo and UCBMSCs, the skin appendages, blood vessels, and nerves were regenerated, the wound closure rate was significantly accelerated, and scarring was reduced54. Li et al.23 used an aging nude mouse model and HDF model to prove that UC-MSCs can increase the thickness of aging skin and the production of matrix collagen fibers, increase the proliferation and migration of human dermal fibroblasts (HDFs), and promote skin regeneration. In addition, an interesting study showed that UC-MSCs can also be used as carriers for gene transfer and drug delivery to enhance the expression of the target gene and can interact with cytokines to change the secretion level to enhance regeneration. The Wnt protein is the key mediator of skin development. Researchers obtained conditioned medium (Wnt-CM) containing Wnt7a from the supernatant of UC-MSCs overexpressing Wnt7a and injected it into the wounds of mice. It was found that the supernatant promoted wound healing, induced hair follicle regeneration, and enhanced the expression of the ECM and the migration of fibroblasts55.
Inflammation is a pathophysiological reaction after tissue injury and a protective defense response of tissues and organs to harmful stimuli. A certain degree of inflammation is beneficial, but excessive inflammation can lead to local tissue cell necrosis and dysfunction, and persistent chronic inflammation can hinder the growth or regeneration of functional cells in tissue56,57. Moreover, the human body is always exposed to various stimuli, and long-term inflammatory stimulation eventually leads to the degeneration of the structure and function of tissues and organs. Therefore, the reduction in inflammatory reactions may be beneficial to the regeneration of tissues and organs. Experiments showed that the gradual accumulation of senescent cells in the body increased the release of proinflammatory factors such as IL-6, IL-8, and TNF- and further promoted the occurrence of senescence58. Photoaging is the main form of skin aging. Long-term exposure to UVR accelerates the aging of skin under the action of inflammatory cells and proinflammatory cytokines59.
UC-MSCs exert their anti-inflammatory effect mainly by secreting cytokines, growth factors, anti-inflammatory factors, and exocrine factors to reduce the inflammatory response and enhance tissue repair. They can also directly interact with the surface molecules of immune cells and regulate the downstream pathways of immune cells, thus affecting cell proliferation, effector production, and cell survival60. Several Korean researchers have used antibody arrays to evaluate the concentrations of growth factors and cytokines in UC-MSC-CM. The results showed that UC-MSC-CM contained high concentrations of anti-inflammatory-related growth factors and cytokines, including EGF, TIMP-1, IGFBP-7, thrombin reactive protein-1, fibrinogen, and fibronectin61. The authors further tested the anti-inflammatory activity of UC-MSCs-CM on HaCaT cells stimulated with TNF- and INF-. The results showed that UC-MSC-CM had an inhibitory effect on the inflammatory cytokines TARC, TNF-, IL-1, and IL-6 and suggested that UC-MSC-CM had an anti-inflammatory effect. Li et al.62 confirmed that UCMSC treatment can reduce the expression levels of the proinflammatory cytokines TNF-, IL-1, and IL-6 in an LPS-induced rat model and concluded that UCMSC treatment can reduce systemic inflammation associated with LPS.
We know that continuous inflammation stimulates tissue fibroplasia, leading to tissue and organ fibrosis. Liu et al.63 used a rat model of renal interstitial fibrosis to evaluate the effect of UCMSC-CM on tubulointerstitial inflammation and fibrosis. The results showed that UCMSC-CM reduced the deposition of ECM, the infiltration of inflammatory cells, and the release of inflammatory factors in renal fibrosis by inhibiting the activation of the TLR4/NFB signaling pathway. Chens team64 injected UC-MSCs subcutaneously into psoriatic arthritis model mice and found that UC-MSCs inhibited skin inflammation and significantly ameliorated the pathological features of mice.
Oxidation is a process in which substances are decomposed to release energy and take place in the body regularly. When the body is in a normal physiological state, the oxidation capacity and antioxidant capacity are in dynamic balance. Once the production of free radicals (such as ROS) exceeds the bodys antioxidant capacity, the redox state is out of balance, and oxidative stress is induced65,66. Oxidative stress is accompanied by the processes of cell injury, inflammation, and metabolic disorders, which are involved in the pathology of many diseases and are considered to be the cause of aging. It has been reported that excessive ROS can directly oxidize DNA, proteins, and lipids, resulting in DNA damage, mitochondrial damage, protein damage, cell senescence, and even death67,68,69. According to the theory of free radical aging, ROS are mainly produced as a result of cell metabolism dysfunction and UVR; are generated by the mitochondrial electron transport chain, peroxisomes, and endoplasmic reticulum; and play a major role in skin aging70. ROS can activate the MAPK signaling pathway through a series of intermediates to promote the production of MMPs. MMPs can degrade collagen and elastin, resulting in increased and deepened skin wrinkles and a lack of elasticity71. ROS and the activated MAPK signaling pathway can also activate NFB, mediate the expression of inflammatory cytokines, further promote the production of ROS, and accelerate skin aging72,73.
There are few reports on the antioxidant effect of UC-MSCs on skin aging. Some scholars believe that UC-MSCs can directly alleviate mitochondrial dysfunction, thus blocking the production of more free radicals from dysfunctional mitochondria that accelerate aging, but the specific mechanism is not clear74. However, an increasing number of researchers have observed the antioxidant stress effect of UC-MSCs in aging animal models. Recently, it was reported that after UCMSC treatment of D-galactose-induced skin aging model nude mice, the levels of superoxide dismutase (SOD) in skin tissue increased significantly, while the levels of malondialdehyde decreased significantly, essentially returning to normal levels23. It is suggested that UCMSC treatment can enhance the ability of cells to scavenge free radicals, improve the antioxidant stress function of skin, and play a positive role in reducing cell senescence caused by oxidative stress. However, while the antioxidant effects of UCMSC treatment have been observed, the underlying mechanism is still not completely clear. Some scholars believe that UC-MSCs play an antioxidant stress role by directly scavenging free radicals, secreting bioactive enzymes, and regulating the function of mitochondria, but there is insufficient evidence75.
Advanced glycation end products (AGEs) are the products of nonenzymatic glycosylation and oxidation of proteins and lipids, which accumulate in inflammatory environments and during aging. The accumulated AGEs easily interact with collagen fibers in the dermis to produce glycosylated collagen in the body. The structural changes of glycosylated collagen increase skin fragility and decrease skin strength so that its biological function is reduced76,77. A new study showed that UC-MSCs can protect fibroblasts from AGE cytotoxicity by secreting cytokines and activating the PI3K/AKT/PTEN pathway78.
Senile diabetes is a very common chronic disease related to aging. The difficulty of healing skin wounds in patients with diabetes is a problem that urgently needs to be solved78. An in-depth study of the pathogenesis of diabetic dermatopathy found the root cause of diabetic wound formation and healing difficulty to be the accumulation of AGEs in the dermis. However, to date, only a few effective methods can inhibit and remove AGEs in wounds, and the emergence of MSCs therapy brings great hope to these diabetic patients79,80,81,82. Many researchers have studied the promoting effect of mesenchymal stromal cells from different sources on diabetic wound healing. The results show that BMSCs and UC-MSCs can effectively promote diabetic skin wound healing83,84.
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Role of umbilical cord mesenchymal stromal cells in skin rejuvenation | npj Regenerative Medicine - Nature.com
Exosomes and Stem Cells Are the Future of Anti-Aging – NewBeauty Magazine
Our skin is a story, told chapter by chapter as we age. But what if we could rewrite it? That seemingly sci-fi future is already here thanks to cutting-edge technologies like exosomes, stem cells and bio-identical hormones. Changing the approach from preservation to regeneration, these new treatments and technologies are changing the narrative around aging.
Thats how New York dermatologistJulie Russak, MDdescribes the shift in her practice since employing these tools. The aging process leaves its mark on our skin, but advancements in regenerative medicine are rewriting the narrative, she says. Exosomes and stem cells, previously confined to the realm of science fiction, are now emerging as powerful tools in my dermatology arsenal.
The next big thing in dermatology, the exosome, is essentially a delivery system. Imagine microscopic envelopes meticulously created by stem cells, packed with genetic
instructions and protein packages, Dr. Russak explains. These are exosomes.
Just like envelopes, whats contained inside is whats really interesting.
Exosomes deliver key signaling molecules, instructing fibroblasts, or skin cells, to ramp up collagen production, Dr. Russak says. This translates to thicker, firmer skin with visibly reduced wrinkles and fine lines.
They offer an answer to sun damage as well.
Sun damage wreaks havoc on our skin, but exosomes offer a cellular-level repair kit, Dr. Russak explains. They promote the regeneration of UV-damaged structures, mitigating the appearance of sunspots and uneven tone. Unlike broad-spectrum approaches, exosomes excel at precision. They hone in on specific skin cells, ensuring their restorative cargo reaches the areas that need it most, maximizing effectiveness and minimizing potential side effects.
Stem cells are the master cells of regeneration, says Dr. Russak. These unique cells possess the remarkable ability to self-renew and differentiate into various specialized cell types, including those crucial for healthy skin.
In dermatology, stem cells are utilized to regenerate tissue and promote collagen production, which makes them perfect for tackling things like age spots, skin firmness and even hair loss. Theyre also employed during in-office treatments like microneedling and laser treatments to expedite recovery and maximize rejuvenation. Because they can be directed to become different kinds of skin cells, stem cells are especially versatile to dermatologists.
We use this versatility in dermatological treatments to replace damaged or aging cells with new, healthy cells, Dr. Russak explains. Both exosomes and stem cell treatments represent a shift towards a more regenerative and holistic approach in dermatology. Rather than merely masking the symptoms of aging skin, these treatments aim to restore the skins natural ability to heal and renew itself.
In the world of anti-aging, the name Dr. David Sinclair is a big one. Australian-American biologist and professor of genetics at Harvard Medical School, Dr. Sinclair has published pivotal work on the science of aging and longevity.
These innovative methods are partly inspired by groundbreaking research in cellular health and aging, including the work of Dr. David Sinclair, Dr. Russak explains. In the field of dermatology, theres a growing trend toward using regenerative medicine to slow aging, with a focus on treatments like exosomes, stem cell therapies and bio-identical hormone replacement therapy (BHRT).
Using exosomes in procedures like microneedling is just the beginning.
We are incorporating topical treatments with peptides and growth factors, as well as injectable therapies like PRP (Platelet-Rich Plasma) and biostimultary molecules like PLLC and CaHa to stimulate the skins natural repair processes, Dr. Russak explains.
Alongside things like diet, lifestyle change and nutraceuticals like NAD+ boosters, dermatologists aim to improve skin, slow down aging and potentially even reverse hair loss.
Unlike many traditional methods of anti-aging, exosomes and stem cells are a natural path to rejuvenation. Rather than masking signs of damage, these treatments are encouraging your body to do the work itself.
Its important to have realistic expectations and understand that multiple treatments may be necessary, Dr. Russak says. Rigorous clinical research is ongoing and long-term data is still needed to definitively establish the safety and efficacy of these treatments. While the future holds immense promise, I remain grounded in evidence-based practice, incorporating these innovations only when robust scientific data supports their benefit.
Due to the newness of these treatments, more long-term studies are needed to fully understand their safety and efficacy. Because the regulatory side of things havent caught up to the technology, practitioners also must consider how to ethically source stem cells and exosomes.
Patients should ensure treatments are performed by qualified professionals and that the products used are compliant with regulatory standards, Dr. Russak explains. As we are just at the very beginning of this exciting field, practitioners and patients need to exercise due diligence when considering these treatments.
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Exosomes and Stem Cells Are the Future of Anti-Aging - NewBeauty Magazine
Leukaemia signs and symptoms: How to detect, treat the aggressive blood cancer – Hindustan Times
Leukaemia signs and symptoms: How to detect, treat the aggressive blood cancer Hindustan Times
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Leukaemia signs and symptoms: How to detect, treat the aggressive blood cancer - Hindustan Times
Adult stem cell – Wikipedia
Multipotent stem cell in the adult body
Adult stem cells are undifferentiated cells, found throughout the body after development, that multiply by cell division to replenish dying cells and regenerate damaged tissues. Also known as somatic stem cells (from Greek , meaning of the body), they can be found in juvenile, adult animals, and humans, unlike embryonic stem cells.
Scientific interest in adult stem cells is centered around two main characteristics. The first of which, being their ability to divide or self-renew indefinitely, and secondly, their ability to generate all the cell types of the organ from which they originate, potentially regenerating the entire organ from a few cells.[1] Unlike embryonic stem cells, the use of human adult stem cells in research and therapy is not considered to be controversial, as they are derived from adult tissue samples rather than human embryos designated for scientific research. The main functions of adult stem cells are to replace cells that are at risk of possibly dying as a result of disease or injury and to maintain a state of homeostasis within the cell.[2] There are three main methods to determine if the adult stem cell is capable of becoming a specialized cell.[2] The adult stem cell can be labeled in vivo and tracked, it can be isolated and then transplanted back into the organism, and it can be isolated in vivo and manipulated with growth hormones.[2] They have mainly been studied in humans and model organisms such as mice and rats.
A stem cell possesses two properties:
To ensure self-renewal, stem cells undergo two types of cell division (see Stem cell division and differentiation diagram). Symmetric division gives rise to two identical daughter stem cells, whereas asymmetric division produces one stem cell and one progenitor cell with limited self-renewal potential. Progenitors can go through several rounds of cell division before finally differentiating into a mature cell. It is believed that the molecular distinction between symmetric and asymmetric divisions lies in differential segregation of cell membrane proteins (such as receptors) and their associated proteins between the daughter cells.[5]
Under normal conditions, tissue stem cells divide slowly and infrequently. They exhibit signs of quiescence, or reversible growth arrest.[6] The niche the stem cell is found in plays a large role in maintaining quiescence.[6] Perturbed niches cause the stem cell to begin actively dividing again to replace lost or damaged cells until the niche is restored. In hematopoietic stem cells, the MAPK/ERK pathway and PI3K/AKT/mTOR pathway regulate this transition.[7] The ability to regulate the cell cycle in response to external cues helps prevent stem cell exhaustion, or the gradual loss of stem cells following an altered balance between dormant and active states. Infrequent cell divisions also help reduce the risk of acquiring DNA mutations that would be passed on to daughter cells.
Discoveries in recent years have suggested that adult stem cells might have the ability to differentiate into cell types from different germ layers. For instance, neural stem cells from the brain, which are derived from ectoderm, can differentiate into ectoderm, mesoderm, and endoderm.[8] Stem cells from the bone marrow, which is derived from mesoderm, can differentiate into liver, lung, GI tract and skin, which are derived from endoderm and mesoderm.[9] This phenomenon is referred to as stem cell transdifferentiation or plasticity. It can be induced by modifying the growth medium when stem cells are cultured in vitro or transplanting them to an organ of the body different from the one they were originally isolated from. There is yet no consensus among biologists on the prevalence and physiological and therapeutic relevance of stem cell plasticity. More recent findings suggest that pluripotent stem cells may reside in blood and adult tissues in a dormant state.[10] These cells are referred to as "Blastomere Like Stem Cells" (BLSCs)[11] and "very small embryonic like" (VSEL) stem cells, and display pluripotency in vitro.[10] As BLSCs and VSEL cells are present in virtually all adult tissues, including lung, brain, kidneys, muscles, and pancreas,[12] co-purification of BLSCs and VSEL cells with other populations of adult stem cells may explain the apparent pluripotency of adult stem cell populations. However, recent studies have shown that both human and murine VSEL cells lack stem cell characteristics and are not pluripotent.[13][14][15][16]
Stem cell function becomes impaired with age, and this contributes to progressive deterioration of tissue maintenance and repair.[17] A likely important cause of increasing stem cell dysfunction is age-dependent accumulation of DNA damage in both stem cells and the cells that comprise the stem cell environment.[17] (See also DNA damage theory of aging.)
Adult stem cells can, however, be artificially reverted to a state where they behave like embryonic stem cells (including the associated DNA repair mechanisms). This was done with mice as early as 2006[citation needed] with future prospects to slow down human aging substantially. Such cells are one of the various classes of induced stem cells.
Adult stem cell research has been focused on uncovering the general molecular mechanisms that control their self-renewal and differentiation.
Hematopoietic stem cells (HSCs) are stem cells that can differentiate into all blood cells.[21] This process is called haematopoiesis.[22] Hematopoietic stem cells are found in the bone marrow and umbilical cord blood.[23] The HSC are generally dormant when found in adults due to their nature.[24]
Mammary stem cells provide the source of cells for growth of the mammary gland during puberty and gestation and play an important role in carcinogenesis of the breast.[25] Mammary stem cells have been isolated from human and mouse tissue as well as from cell lines derived from the mammary gland. Single such cells can give rise to both the luminal and myoepithelial cell types of the gland and have been shown to have the ability to regenerate the entire organ in mice.[25]
Intestinal stem cells divide continuously throughout life and use a complex genetic program to produce the cells lining the surface of the small and large intestines.[26] Intestinal stem cells reside near the base of the stem cell niche, called the crypts of Lieberkuhn. Intestinal stem cells are probably the source of most cancers of the small intestine and colon.[27]
Mesenchymal stem cells (MSCs) are of stromal origin and may differentiate into a variety of tissues. MSCs have been isolated from placenta, adipose tissue, lung, bone marrow and blood, Wharton's jelly from the umbilical cord,[28] and teeth (perivascular niche of dental pulp and periodontal ligament).[29] MSCs are attractive for clinical therapy due to their ability to differentiate, provide trophic support, and modulate innate immune response.[28] These cells have the ability to differentiate into various cell types such as osteoblasts, chondroblasts, adipocytes, neuroectodermal cells, and hepatocytes.[30] Bioactive mediators that favor local cell growth are also secreted by MSCs. Anti-inflammatory effects on the local microenvironment, which promote tissue healing, are also observed. The inflammatory response can be modulated by adipose-derived regenerative cells (ADRC) including mesenchymal stem cells and regulatory T-lymphocytes. The mesenchymal stem cells thus alter the outcome of the immune response by changing the cytokine secretion of dendritic and T-cell subsets. This results in a shift from a pro-inflammatory environment to an anti-inflammatory or tolerant cell environment.[31][32]
Endothelial stem cells are one of the three types of multipotent stem cells found in the bone marrow. They are a rare and controversial group with the ability to differentiate into endothelial cells, the cells that line blood vessels as well as lymphatic vessels. Endothelial stem cells are an important aspect in the vascular network, even influencing the motion relating to white blood cells.
The existence of stem cells in the adult brain has been postulated following the discovery that the process of neurogenesis, the birth of new neurons, continues into adulthood in rats.[33] The presence of stem cells in the mature primate brain was first reported in 1967.[34] It has since been shown that new neurons are generated in adult mice, songbirds and primates, including humans. Normally, adult neurogenesis is restricted to two areas of the brain the subventricular zone, which lines the lateral ventricles, and the dentate gyrus of the hippocampal formation.[35] Although the generation of new neurons in the hippocampus is well established, the presence of true self-renewing stem cells there has been debated.[36] Under certain circumstances, such as following tissue damage in ischemia, neurogenesis can be induced in other brain regions, including the neocortex.
Neural stem cells are commonly cultured in vitro as so called neurospheres floating heterogeneous aggregates of cells, containing a large proportion of stem cells.[37] They can be propagated for extended periods of time and differentiated into both neuronal and glia cells, and therefore behave as stem cells. However, some recent studies suggest that this behaviour is induced by the culture conditions in progenitor cells, the progeny of stem cell division that normally undergo a strictly limited number of replication cycles in vivo.[38] Furthermore, neurosphere-derived cells do not behave as stem cells when transplanted back into the brain.[39]
Neural stem cells share many properties with haematopoietic stem cells (HSCs). Remarkably, when injected into the blood, neurosphere-derived cells differentiate into various cell types of the immune system.[40]
Olfactory adult stem cells have been successfully harvested from the human olfactory mucosa cells, which are found in the lining of the nose and are involved in the sense of smell.[41] If they are given the right chemical environment, these cells have the same ability as embryonic stem cells to develop into many different cell types. Olfactory stem cells hold the potential for therapeutic applications and, in contrast to neural stem cells, can be harvested with ease without harm to the patient. This means they can be easily obtained from all individuals, including older patients who might be most in need of stem cell therapies.
Hair follicles contain two types of stem cells, one of which appears to represent a remnant of the stem cells of the embryonic neural crest. Similar cells have been found in the gastrointestinal tract, sciatic nerve, cardiac outflow tract and spinal and sympathetic ganglia. These cells can generate neurons, Schwann cells, myofibroblast, chondrocytes and melanocytes.[42][43]
Multipotent stem cells with a claimed equivalency to embryonic stem cells have been derived from spermatogonial progenitor cells found in the testicles of laboratory mice by scientists in Germany[44][45][46] and the United States,[47][48][49][50] and, a year later, researchers from Germany and the United Kingdom confirmed the same capability using cells from the testicles of humans.[51] The extracted stem cells are known as human adult germline stem cells (GSCs)[52]
Multipotent stem cells have also been derived from germ cells found in human testicles.[53]
Adult stem cell treatments have been used for many years to successfully treat leukemia and related bone/blood cancers utilizing bone marrow transplants.[54] The use of adult stem cells in research and therapy is not considered as controversial as the use of embryonic stem cells, because the production of adult stem cells does not require the destruction of an embryo.
Early regenerative applications of adult stem cells has focused on intravenous delivery of blood progenitors known as Hematopetic Stem Cells (HSC's). CD34+ hematopoietic Stem Cells have been clinically applied to treat various diseases including spinal cord injury,[55] liver cirrhosis[56] and Peripheral Vascular disease.[57] Research has shown that CD34+ hematopoietic Stem Cells are relatively more numerous in men than in women of reproductive age group among spinal cord Injury victims.[58] Other early commercial applications have focused on Mesenchymal Stem Cells (MSCs). For both cell lines, direct injection or placement of cells into a site in need of repair may be the preferred method of treatment, as vascular delivery suffers from a "pulmonary first pass effect" where intravenous injected cells are sequestered in the lungs.[59] Clinical case reports in orthopedic applications have been published. Wakitani has published a small case series of nine defects in five knees involving surgical transplantation of mesenchymal stem cells with coverage of the treated chondral defects.[60] Centeno et al. have reported high field MRI evidence of increased cartilage and meniscus volume in individual human clinical subjects as well as a large n=227 safety study.[61][62][63] Many other stem cell based treatments are operating outside the US, with much controversy being reported regarding these treatments as some feel more regulation is needed as clinics tend to exaggerate claims of success and minimize or omit risks.[64]
The therapeutic potential of adult stem cells is the focus of much scientific research, due to their ability to be harvested from the parent body that is females during the delivery.[65][66][67] In common with embryonic stem cells, adult stem cells have the ability to differentiate into more than one cell type, but unlike the former they are often restricted to certain types or "lineages". The ability of a differentiated stem cell of one lineage to produce cells of a different lineage is called transdifferentiation. Some types of adult stem cells are more capable of transdifferentiation than others, but for many there is no evidence that such a transformation is possible. Consequently, adult stem therapies require a stem cell source of the specific lineage needed, and harvesting and/or culturing them up to the numbers required is a challenge.[68][69] Additionally, cues from the immediate environment (including how stiff or porous the surrounding structure/extracellular matrix is) can alter or enhance the fate and differentiation of the stem cells.[70]
Pluripotent stem cells, i.e. cells that can give rise to any fetal or adult cell type, can be found in a number of tissues, including umbilical cord blood.[71] Using genetic reprogramming, pluripotent stem cells equivalent to embryonic stem cells have been derived from human adult skin tissue.[72][73][74][75] Other adult stem cells are multipotent, meaning there are several limited types of cell they can become, and are generally referred to by their tissue origin (such as mesenchymal stem cell, adipose-derived stem cell, endothelial stem cell, etc.).[76][77] A great deal of adult stem cell research has focused on investigating their capacity to divide or self-renew indefinitely, and their potential for differentiation.[78] In mice, pluripotent stem cells can be directly generated from adult fibroblast cultures.[79]
In recent years, acceptance of the concept of adult stem cells has increased. There is now a hypothesis that stem cells reside in many adult tissues and that these unique reservoirs of cells not only are responsible for the normal reparative and regenerative processes but are also considered to be a prime target for genetic and epigenetic changes, culminating in many abnormal conditions including cancer.[80][81] (See cancer stem cell for more details.)
Adult stem cells express transporters of the ATP-binding cassette family that actively pump a diversity of organic molecules out of the cell.[82] Many pharmaceuticals are exported by these transporters conferring multidrug resistance onto the cell. This complicates the design of drugs, for instance neural stem cell targeted therapies for the treatment of clinical depression.
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Adult stem cell - Wikipedia
Stem cells: a brief history and outlook – Science in the News
Stem cells have been the object of much excitement and controversy amongst both scientists and the general population. Surprisingly, though, not everybody understands the basic properties of stem cells, let alone the fact that there is more than one type of cell that falls within the stem cell category. Here, Ill lay out the basic concepts of stem cell biology as a background for understanding the stem cell research field, where it is headed, and the enormous promise it offers for regenerative medicine.
Fertilization of an egg cell by a sperm cell results in the generation of a zygote, the single cell that, upon a myriad of divisions, gives rise to our whole body. Because of this amazing developmental potential, the zygote is said to be totipotent. Along the way, the zygote develops into the blastocyst, which implants into the mothers uterus. The blastocyst is a structure comprising about 300 cells that contains two main regions: the inner cell mass (ICM) and the trophoblast. The ICM is made of embryonic stem cells (ES cells), which are referred to as pluripotent. They are able to give rise to all the cells in an embryo proper, but not to extra-embryonic tissues, such as the placenta. The latter originate from the trophoblast [].
Even though it is hard to pinpoint exactly when or by whom what we now call stem cells were first discovered, the consensus is that the first scientists to rigorously define the key properties of a stem cell were Ernest McCulloch and James Till. In their pioneering work in mice in the 1960s, they discovered the blood-forming stem cell, the hematopoietic stem cell (HSC) [2, 3]. By definition, a stem cell must be capable of both self-renewal (undergoing cell division to make more stem cells) and differentiation into mature cell types. HSCs are said to be multipotent, as they can still give rise to multiple cell types, but only to other types of blood cells (see Figure 1, left column). They are one of many examples of adult stem cells, which are tissue-specific stem cells that are essential for organ maintenance and repair in the adult body. Muscle, for instance, also possesses a population of adult stem cells. Called satellite cells, these muscle cells are unipotent, as they can give rise to just one cell type, muscle cells.
Therefore, the foundations of stem cell research lie not with the famous (or infamous) human embryonic stem cells, but with HSCs, which have been used in human therapy (such as bone marrow transplants) for decades. Still, what ultimately fueled the enormous impact that the stem cell research field has today is undoubtedly the isolation and generation of pluripotent stem cells, which will be the main focus of the remainder of the text.
Figure 1: Varying degrees of stem cell potency. Left: The fertilized egg (totipotent) develops into a 300-cell structure, the blastocyst, which contains embryonic stem cells (ES cells) at the inner cell mass (ICM). ES cells are pluripotent and can thus give rise to all cell types in our body, including adult stem cells, which range from multipotent to unipotent. Right: An alternative route to obtain pluripotent stem cells is the generation of induced pluripotent stem cells (iPS cells) from patients. Cell types obtained by differentiation of either ES cell (Left) or iPS cells (Right) can then be studied in the dish or used for transplantation into patients. Figure drawn by Hannah Somhegyi.
Martin Evans (Nobel Prize, 2007) and Matt Kauffman were the first to identify, isolate and successfully culture ES cells using mouse blastocysts in 1981 []. This discovery opened the doors to the creation of murine genetic models, which are mice that have had one or several of their genes deleted or otherwise modified to study their function in disease []. This is possible because scientists can modify the genome of a mouse in its ES cells and then inject those modified cells into mouse blastocysts. This means that when the blastocyst develops into an adult mouse, every cell its body will have the modification of interest.
The desire to use stem cells unique properties in medicine was greatly intensified when James Thomson and collaborators first isolated ES cells from human blastocysts []. For the first time, scientists could, in theory, generate all the building blocks of our body in unlimited amounts. It was possible to have cell types for testing new therapeutics and perhaps even new transplantation methods that were previously not possible. Yet, destroying human embryos to isolate cells presented ethical and technical hurdles. How could one circumvent that procedure? Sir John Gurdon showed in the early 1960s that, contrary to the prevalent belief back then, cells are not locked in their differentiation state and can be reverted to a more primitive state with a higher developmental potential. He demonstrated this principle by injecting the nucleus of a differentiated frog cell into an egg cell from which the nucleus had been removed. (This is commonly known as reproductive cloning, which was used to generate Dolly the Sheep.) When allowed to develop, this egg gave rise to a fertile adult frog, proving that differentiated cells retain the information required to give rise to all cell types in the body. More than forty years later, Shinya Yamanaka and colleagues shocked the world when they were able to convert skin cells called fibroblasts into pluripotent stem cells by altering the expression of just four genes []. This represented the birth of induced pluripotent stem cells, or iPS cells (see Figure 1, right column). The enormous importance of these findings is hard to overstate, and is perhaps best illustrated by the fact that, merely six years later, Gurdon and Yamanaka shared the Nobel Prize in Physiology or Medicine 2012 [].
Since the generation of iPS cells was first reported, the stem cell eld has expanded at an unparalleled pace. Today, these cells are the hope of personalized medicine, as they allow one to capture the unique genome of each individual in a cell type that can be used to generate, in principle, all cell types in our body, as illustrated on the right panel of Figure 1. The replacement of diseased tissues or organs without facing the barrier of immune rejection due to donor incompatibility thus becomes approachable in this era of iPS cells and is the object of intense research [].
The first proof-of-principle study showing that iPS cells can potentially be used to correct genetic diseases was carried out in the laboratory of Rudolf Jaenisch. In brief, tail tip cells from mice with a mutation causing sickle cell anemia were harvested and reprogrammed into iPS cells. The mutation was then corrected in these iPS cells, which were then differentiated into blood progenitor cells and transplanted back into the original mice, curing them []. Even though iPS cells have been found not to completely match ES cells in some instances, detailed studies have failed to find consistent differences between iPS and ES cells []. This similarity, together with the constant improvements in the efficiency and robustness of generating iPS cells, provides bright prospects for the future of stem cell research and stem cell-based treatments for degenerative diseases unapproachable with more conventional methods.
Leonardo M. R. Ferreira is a graduate student in Harvard Universitys Department of Molecular and Cellular Biology
[] Stem Cell Basics: http://stemcells.nih.gov/info/basics/Pages/Default.aspx
[] Becker, A. J., McCulloch, E.A., Till, J.E. Cytological demonstration of the clonal nature of spleen colonies derived from transplanted mouse marrow cells. Nature 1963. 197: 452-4
[] Siminovitch, L., McCulloch, E.A., Till, J.E. The distribution of colony-forming cells among spleen colonies. J Cell Comp Physiol 1963, 62(3): 327-336
[] Evans, M. J. and Kaufman, M. Establishment in culture of pluripotential stem cells from mouse embryos. Nature 1981, 292: 151156
[] Simmons, D. The Use of Animal Models in Studying Genetic Disease: Transgenesis and Induced Mutation. Nature Education 2008,1(1):70
[] Thomson, J. A. et al. Embryonic stem cell lines derived from human blastocysts. Science 1998, 282(5391): 1145-1147
[] Takahashi, K. and Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006. 126(4): 663-76
[] The Nobel Prize in Physiology or Medicine 2012:
[] Ferreira, L.M.R. and Mostajo-Radji, M.A. How induced pluripotent stem cells are redefining personalized medicine. Gene 2013. 520(1): 1-6 [] Hanna J. et al. Treatment of sickle cell anemia mouse model with iPS cells generated from autologous skin. Science 2007. 318: 1920-1923
[] Yee,J.Turning Somatic Cells into Pluripotent Stem Cells.Nature Education 2010.3(9):25
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Stem cells: a brief history and outlook - Science in the News
What are totipotent stem cells & what can they do? – The Niche
Sometimes patients or my students ask me, What are the best stem cells? what information are they looking for?
I think they often are looking for the most powerful stem cells so perhaps they should be asking, What are totipotent stem cells?
Other times it seems what patients specifically want to know is what might be the best stem cells for their particular condition. The answer to that is, of course, going to depend on many factors. Im a long-time stem cell biologist so I can give them that perspective, but this should be something they discuss primarily with their physician
Todays post focuses on the question of what totipotent cells are all about and addresses more specific questions about them, including why so far there seem to be fewer clinical applications for them as compared to most other stem cell types.
Every year I give a lecture here at UC Davis School of Medicine for my medical students about stem cells. Some students seem especially fascinated by totipotent stem cells. Their interest probably is piqued because these are the most powerful cells. For example, recently a student asked me, Professor Knoepfler, are there any types of cells that totipotent stem cells cannot make?
As their name implies, totipotent stem cells are entirely potent or all-powerful from a cellular perspective. What that means is that these cells can make any other cells in the developing body in utero as well as the special cells and tissues needed during development. Those latter structures include placenta and umbilical cord.
For example, the classic kind of totipotent cell is the fertilized egg, also called a zygote. In the animal world, a newly pregnant bear has a zygote that will develop in its uterus that is totipotent. That bears zygote can make the actual new eventual baby bear including all of the several hundred kinds of bear cells and also the placenta and umbilical cord that the fetal bear will need in utero. The same goes for a totipotent human zygote. Also the zygote of a dog, cat, and so on.
You can see examples of real human totipotent stem cells in the image above of early human embryos at the 2- and 4-cell stages at the top of the figure. This material is excerpted from my book on stem cells, Stem Cells: An Insiders Guide.
Interestingly, as normal early embryo development proceeds and the fertilized egg/zygote goes from just being that one cell to divide to make 2 cells and 4 cells and then 8 cells, it is thought that all of the cells are still totipotent. What this means is that if, for example, an 8-cell human embryo for whatever reason breaks into 2 pieces of 3 and 5 cells or 1 and 7 cells, in many cases those separate totipotent cells will go on to make 2 separate embryos and ultimately babies. Congrats, you have twins. Each twin in that case can also develop their own umbilical cord and placenta too, although they sometimes share. This is all possible because these very early embryonic cells are totipotent.
After the 8-cell stage or so, the embryonic cells start to lose their totipotency and become either multipotent (can make only a few types of cells) or pluripotent stem cells. The latter are the second most powerful stem cells so lets briefly talk about them next.
Pluripotent stem cells are almost as flexible as those with totipotency, but not quite. See video above. The pluripotent cells inside a developing early embryo of a specific species can make all the cells that will become the actual body of a person, a bear, or many other animals, again depending on which animal is involved. These pluripotent cells cannot, however, make the placenta or umbilical cord. This one thing that they cannot do is what makes them different than totipotent cells.
Pluripotent stem cells include some of the most well known kinds of stem cells out there including embryonic stem cells (ES cells) and induced pluripotent stem cells, also known as IPS cells.
Pluripotent stem cells are often grown in labs and differentiated into a wide variety of other types of more specialized cells such as neurons, muscle cells including beating heart muscle (see video below), lung cells and more. Some have claimed that certain IPS cells can be totipotent but that is still being debated.
Both ES cells and IPS cells can also be made into what are called organoids, which are miniature versions of normal organs. For instance, my lab makes brain organoids regularly from IPS cells. Organoids are a very powerful technology in many ways so as being a way to find new drugs for specific diseases.
I have not heard yet of specific clinical applications for these most powerful stem cells. On the global clinical trial database Clinicaltrials.gov I found just a single trial that mentions the word totipotent and it isnt related to using such cells as a treatment.
Most of the clinical potential seems to be focused on adult stem cells as well as IPS cells and ES cells. One could imagine that totipotent stem cells will be useful for research on human development and potentially infertility.
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What are totipotent stem cells & what can they do? - The Niche
Certain Foods Discovered to Increase Stem Cells, Cell Regeneration
William W. Li MD writes in his book Eat to Beat Disease, Your immune cells are regenerated every seven days, so if your stem cells disappeared, youd likely die of an infection soon after. However, you can increase your stem cells by taking in the right foods.
We develop from stem cells. When the fathers sperm meets the mothers egg, a fertilized egg is formed. It continues to divide and by day three to five develops into an embryoconsisting of about 150 stem cells in the mothers uterus. Later, these stem cells in the embryo continue to split and form various tissues and organs in the human body. There are more than two hundred different kinds of cells in the human body, all of which grow from stem cells.
Stem cells are not only present at the embryonic development stage. When babies are born, they carry a large number of stem cells within their bodies. The average person has about 37.2 trillion cells, including about 750 million stem cells, which account for 0.002 percent of the total cells (Page 27, Eat to Beat Disease).These stem cells are stored in various parts of the body, ready to regenerate or repair body tissues and organs.
Dr. William Li, the author of Eat to Beat Disease, president of the Angiogenesis Foundation and a Harvard-trained medical doctor, elaborated on the role of stem cells in an interview with The Epoch Times. Li said stem cells are mainly stored in the bone marrow, though also found in the bodys fat, skin, hair follicles, and even in the heart. He made an analogy: The human body retains and dispatches stem cells just like we keep unused paint in the garage during renovation, which is ready for use if necessary, say, for wall repair someday.
As all human tissues and organs get renewed constantly, stem cells play a key role in this process. Specifically, we need them to produce new skin to replace damaged skin cells; and to replace damaged cells on the surface of the intestine. Besides, hematopoietic stem cells divide and replace those blood cells that are damaged while operating in the circulatory system. They, too, evolve into types of white and red blood cells, and more.
Interestingly, our small intestine is renewed every two to four days; our lungs and stomach every eight days; our skin every two weeks; our red blood cells every four months; our fat cells every eight years; and our skeleton every ten years. Dr. Li cited an example: The bodys immune cells regenerate every seven days. Therefore, if a persons relevant stem cells disappear, he or she could die soon from an infection (Page 26, Eat to Beat Disease).
In addition, he quoted a Japanese story of nuclear radiation to highlight the critical life-supporting role of stem cells in his book. During the Second World War, the atomic bombardments in the cities of Hiroshima and Nagasaki caused about 200,000 deaths. Afterward, a second wave of deaths hit certain survivors because the ability of their bone marrow to make stem cells had been destroyed due to exposure to radiation. Further, in cancer treatment, chemotherapy and radiotherapy affect the survival of stem cells while destroying cancer cells, putting patients in tremendous pain and challenges (page 26, Eat to Beat Disease).
The human body is born with mechanisms that collaborate seamlessly and automatically to keep life going.
Stem cells come into play when we need to repair cells that are damaged due to various diseases and injuries or replace dysfunctional cells. Figuratively, stem cells are sentinels in the body that are always watching out for health needs and will at times appear at designated locations in preparation for rescue operations.
Dr. Li added that a damaged organ or site in need of repair releases a certain protein that acts as a messenger, calling on stem cells stored in the bone marrow. Then, the cells will respond to the call by leaving the bone marrow and entering the bloodstream. This scenario is almost like a group of bees swarming out of their hive. Together with the blood, stem cells flow to the injured tissue and land at their precise destination. Upon arriving, they begin to divide or transform themselves to regenerate organ or tissue cells.
As is well known, the liver is regenerative. It is the repair and regeneration function of stem cells that explains exactly why the liver can grow back into its original status, even if up to 75 percent of it is removed during surgery.
Likewise, our heart depends on stem cells to keep regenerating constantly, though the rebirth rate is affected by age. A 20-year-old gets about one percent of his or her heart cells renewed every year. However, this rate slows down as he or she gets older. At 75, that person gets only 0.3 percent of the heart cells renewed each year.
Reading that, you may wonder: Will stem cells eventually be depleted as they keep flowing out of the bone marrow? Dr. Lis answer is, Stem cells are capable of regenerating themselves and replenishing their stores in the bone marrow.
Although stem cells in healthy people are equipped with self-replication and replenishment mechanisms, Dr. Li emphasized that there are three scenarios that impair their regenerative and repairing capacity, directly affecting the quality of a persons life.
When smokers inhale cigarette smoke, that leads to a lack of oxygen in the body, which will recruit stem cells into the bloodstream. Habitual smoking keeps consuming the stem cells stored in the bone marrow. A study has shown that the remaining stem cells in smokers bodies have a 75 percent drop in their self-reproduction ability and a 38 percent reduction in their involvement in regeneration. Besides active smoking, Dr. Li added, passive inhalation of secondhand smoke and exposure to heavily polluted air can be equally harmful to stem cells.
Addiction to alcohol kills stem cells. Like smoking, drinking alcohol causes stem cells to be constantly pulled out of the bone marrow into the circulatory system. Meanwhile, stem cells become damaged, negatively affecting their regeneration abilities, according to Dr, Li. Furthermore, drinking alcohol impairs the activity of stem cells in the brain, which in turn affects the hippocampusresponsible for short- and long-term memory.
Both hyperlipidemia and hyperglycemia impair stem cells. Dr. Li says in his bookthat bad cholesterol in the blood, known as low-density lipoprotein (LDL), damages liver cells while good cholesterol, known as high-density lipoprotein (HDL), delays the death of endothelial progenitor cellsa type of stem cell in the blood that maintains the health of blood vessels and repairs their inner layers.
Additionally, diabetes is a stem cell killer. Diabetics are likely to have 47 percent fewer stem cells than normal, with the remaining part of stem cells unable to function properly. This is because hyperglycemia affects stem cell replication and migration, as well as the secretion of survival factors.
Dr. Li also mentioned that high levels of stress and high salt levels in the blood also harm stem cells.
Dr. Li gives advice on how to protect the activity of stem cells in the body and actively mobilize them to repair the body from a dietary perspective. Human experiments have confirmed the following foods, which can increase the number of stem cells.
Dark chocolate contains flavanols that have biological properties. Researchers at the University of California recruited patients with coronary artery disease in a 30-day controlled trial. One group drank hot chocolate low in flavanols (only nine mg per serving) twice a day, and the other group drank hot chocolate high in flavanols (containing 375 mg per serving) twice a day. The results were surprising: the group with high-level flavanol had twice as many stem cells in their blood as that with low-level flavanol, and the formers blood flow improved twice as much as the latter.
A team of Italian researchers divided patients who had mild to moderate hypertension but did not receive medication into two groups. Group A drank plain black tea without sugar and milk twice a day while group B drank other beverages twice a day. One week later, blood tests showed the number of endothelial progenitor cells in the blood in the black-tea group rose by 56 percent, with an improved ability of blood vessel widening.
A Mediterranean diet rich in virgin olive oil is effective in boosting stem cells. A 4-week control study published in The American Journal of Clinical Nutrition showed that compared to those on a diet high in saturated fat or a diet low in fat but high in carbohydrates, those on a Mediterranean diet rich in virgin olive oil showed a significant doubling in their endothelial progenitor cell count in the blood.
Flora Zhao is a health reporter for The Epoch Times. Have a tip? Email her at: flora.zhao@epochtimes.nyc
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Certain Foods Discovered to Increase Stem Cells, Cell Regeneration
Skin Cell – The Definitive Guide | Biology Dictionary
Skin cells are the basic building blocks of the skin; a large, complex organ forms a protective barrier between our insides and the external environment. The most common type of skin cell is the keratinocyte, whose primary function is to form a tough, waterproof layer against UV radiation, harmful chemicals, and infectious agents.
However, the skin also contains highly specialized cells with important immunological, photoprotective, and sensory functions. The term skin cell, therefore, may refer to any of the four major types of cells found in the epidermis (or outer layer) of the skin.
The skin is the largest organ of the human body and has a range of vital functions in supporting survival. The primary function of the skin is to form a physical barrier between the internal environment of an organism and the outside world. This protects internal organs and structures from injury and infection.
The skin also helps to maintain homeostasis by preventing water loss and regulating body temperature. It protects organisms from the damaging effects of UV light and helps to produce vitamin D when exposed to the sun. Finally, the skin functions as a sensory organ, allowing us to perceive touch, temperature changes, and pain.
The skin can perform all of these functions thanks to the highly specialized cells that make up the epidermis (the outermost layer of the skin).
The skin consists of three major layers; the epidermis, the dermis, and the hypodermis (AKA the subcutaneous layer).
The epidermis is the outermost layer of the skin. This waterproof barrier protects the underlying skin layers and other internal structures from injury, UV damage, harmful chemicals, and infections by pathogens such as bacteria, viruses, and fungi. The thickness of the epidermis varies between different parts of the body. In the thin, delicate skin of the eyelids, the epidermis is only around 0.5 mm thick, whereas the more resilient skin of the palms and feet is about 1.5 mm thick.
The dermis is found directly beneath the epidermis and is the thickest of the three skin layers. This layer contains a complex network of specialized structures, including blood vessels, lymph vessels, sweat glands, hair follicles, sebaceous glands, and nerve endings. It also contains collagen and elastin, which are structural proteins that make skin strong and flexible. The main functions of the dermis are to deliver oxygen and nutrients to the epidermis and to help regulate body temperature.
The hypodermis (or subcutaneous layer) is the fatty, innermost layer of the skin. It consists mainly of fat cells and functions as an insulating layer that helps to regulate internal body temperature. The hypodermis also acts as a shock absorber that protects the internal organs from injury.
The term skin cell may refer to any of the four main types of cells found in the epidermis. These are keratinocytes, melanocytes, Langerhans cells, and Merkel cells. Each type of skin cell has a unique role that contributes to the overall structure and function of the skin.
Keratinocytes are the most abundant type of skin cell found in the epidermis and account for around 90-95% of the epidermal cells.
They produce and store a protein called keratin, a structural protein that makes skin, hair, and nails tough and waterproof. The main function of the keratinocytes is to form a strong barrier against pathogens, UV radiation, and harmful chemicals, while also minimizing the loss of water and heat from the body.
Keratinocytes originate from stem cells in the deepest layer of the epidermis (the basal layer) and are pushed up through the layers of the epidermis as new cells are produced. As they migrate upwards, keratinocytes differentiate and undergo structural and functional changes.
The stratum basal (or basal layer) is where keratinocytes are produced by mitosis. Cells in this layer of the epidermis may also be referred to as basal cells. As new cells are continually produced, older cells are pushed up into the next layer of the epidermis; the stratum spinosum.
In the stratum spinosum (or squamous cell layer), keratinocytes take on a spiky appearance and are known as spinous cells or prickle cells. The main function of this epidermal layer is to maintain the strength and flexibility of the skin.
Next, the keratinocytes migrate to the stratum granulosum. Cells in this layer are highly keratinized and have a granular appearance. As they move closer to the surface of the skin, keratinocytes begin to flatten and dry out.
By the time keratinocytes enter the stratum lucidum (AKA the clear layer), they have flattened and died, thanks to their increasing distance from the nutrient-rich blood supply of the stratum basal. The stratum corneum (the outermost layer of the epidermis) is composed of 10 30 layers of dead keratinocytes that are constantly shed from the skin. Keratinocytes of the stratum corneum may also be referred to as corneocytes.
Melanocytes are another major type of skin cell and comprise 5-10% of skin cells in the basal layer of the epidermis.
The main function of melanocytes is to produce melanin, which is the pigment that gives skin and hair its color. Melanin protects skin cells against harmful UV radiation and is produced as a response to sun exposure. In cases of continuous sun exposure, melanin will accumulate in the skin and cause it to become darker i.e., a suntan develops.
Langerhans cells are immune cells of the epidermis and play an essential role in protecting the skin against pathogens. They are found throughout the epidermis but are most concentrated in the stratum spinosum.
Langerhans cells are antigen-presenting cells and, upon encountering a foreign pathogen, will engulf and digest it into protein fragments. Some of these fragments are displayed on the surface of the Langerhans cell as part of its MHCI complex and are presented to nave T cells in the lymph nodes. The T cells are activated to launch an adaptive immune response, and effector T cells are deployed to find and destroy the invading pathogen.
Merkel cells are found in the basal layer of the epidermis and are especially concentrated in the palms, finger pads, feet, and undersides of the toes. They are positioned very close to sensory nerve endings and are thought to function as touch-sensitive cells. Merkel cells allow us to perceive sensory information (such as touch, pressure, and texture) from our external environment.
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Skin Cell - The Definitive Guide | Biology Dictionary
Mesenchymal Stem Cells | Properties, Process, Functions, & Therapies
Mesenchymal Stem Cells: Stem cells are the basic building blocks of tissues and organs in the body. It is important to note that there is no single stem cell that gives rise to them, but in fact, a variety of them coming from different locations in the body and formed at different time periods.
One of the most common type of stem cells is the mesenchymal stem cells (aka MSCs). But what exactly is it? Lets take a closer look.
By definition, mesenchymal stem cells are multipotent cells that can differentiate and mature into different types of cells. Mesenchymal cells are characterized by having long and thin bodies and a very prominent nucleus.
In terms of size, they are relatively smaller than fibrocytes and are quite difficult to observe in histological sections. And overall morphologically speaking, they appear to have no difference from fibroblasts.
A group of mesenchymal stem cells is called a mesenchyme and together, they form the undifferentiated filling of the embryo. Mesenchymal stem cells (or tissue) have a wide distribution in the body.
Like most stem cells, mesenchymal stem cells are capable of self-renewal and differentiation.
Despite its size, the mesenchymal stem cell plays a lot of significant roles within an organism. The following are just some of them.Functions of Mesenchymal Stem Cells (Image Source: frontiersin.org)
1.Suppression of immune cells activation
Aside from being the progenitor of most cells in the body, mesenchymal cells also control the activities of immune cells (i.e. T-lymphocytes, B-lymphocytes, macrophages, mast cells, and neutrophils) during an organ transplant. This is important because it prevents further inflammation and eventual rejection of the transplanted organ.
2. Increase the number of nerve cells
3. Reduction of Cell Death
4. Secretion of neurotrophic and angiogenic factors
Mesenchymal stem cells secrete both neurotrophic and angiogenic factors which are responsible for stabilizing the extracellular matrix (ECM).
5. Increase synaptic connections
When transplanted into the brain, mesenchymal stem cells promote the reduction of free radical levels and enhance the synaptic connections of damaged neurons. In addition to that, they also increase the number of astrocytes (star-shaped cells associated with the formation of functional synapses). As a result, impulses (messages) are being passed on at a faster speed, hence, reactions are also immediate.
6. Increase the myelination of axons
Myelin sheath is the insulating layer that covers the axons of nerve cells. By further enhancing the myelination of axons, mesenchymal cells (similar with above) further increase the speed at which impulses are passed along.
7. Increase the number of blood vessels and astrocytes in the brain
According to a recent study published in the World Journal of Stem Cells, mesenchymal cells are also able to replace and repair any damaged blood vessel in the cerebrum part of the brain. Hence, mesenchymal cells are being viewed as potential therapeutic remedy for stroke patients.
Mesenchymal cells undergo mesengenic process in order to transform into different cell types such as osteocytes (bone cells), chondrocytes (cartilage cells), muscle cells, and others.The Differentiation of Mesenchymal Stem Cells into different types of cells (Image Source: frontiersin.org)
Present-day studies are now paving the way for the further applications of mesenchymal stem cells into numerous clinical measures and techniques. In addition to the natural functions of mesenchymal cells mentioned above, several commercialized products from these cells have already been approved.
Despite their promising effect on overall organism health, the knowledge about mesenchymal stem cells is still incomplete. Hence, further research is still needed to ensure the safety of patients and improve quality control.
Key References
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Mesenchymal Stem Cells | Properties, Process, Functions, & Therapies
Childbirth – Wikipedia
Expulsion of a fetus from the pregnant mother's uterus
Medical condition
Childbirth, also known as labour and delivery, is the ending of pregnancy where one or more babies exits the internal environment of the mother via vaginal delivery or caesarean section.[7] In 2019, there were about 140.11 million births globally.[9] In the developed countries, most deliveries occur in hospitals,[10][11] while in the developing countries most are home births.[12]
The most common childbirth method worldwide is vaginal delivery.[6] It involves four stages of labour: the shortening and opening of the cervix during the first stage, descent and birth of the baby during the second, the delivery of the placenta during the third, and the recovery of the mother and infant during the fourth stage, which is referred to as the postpartum. The first stage is characterized by abdominal cramping or back pain that typically lasts half a minute and occurs every 10 to 30 minutes.[13] Contractions gradually becomes stronger and closer together.[14] Since the pain of childbirth correlates with contractions, the pain becomes more frequent and strong as the labour progresses. The second stage ends when the infant is fully expelled. The third stage is the delivery of the placenta.[15] The fourth stage of labour involves the recovery of the mother, delayed clamping of the umbilical cord, and monitoring of the neonate.[16] As of 2014,[update] all major health organizations advise that immediately following a live birth, regardless of the delivery method, that the infant be placed on the mother's chest (termed skin-to-skin contact), and to delay neonate procedures for at least one to two hours or until the baby has had its first breastfeeding.[17][18][19]
A vaginal delivery is recommended over a cesarean section due to increased risk for complications of a cesarean section and natural benefits of a vaginal delivery in both mother and baby. Various methods may help with pain, such as relaxation techniques, opioids, and spinal blocks.[14] It is best practice to limit the amount of interventions that occur during labour and delivery such as an elective cesarean section, however in some cases a scheduled cesarean section must be planned for a successful delivery and recovery of the mother. An emergency cesarean section may be recommended if unexpected complications occur or little to no progression through the birthing canal is observed in a vaginal delivery.
Each year, complications from pregnancy and childbirth result in about 500,000 birthing deaths, seven million women have serious long-term problems, and 50 million women giving birth have negative health outcomes following delivery, most of which occur in the developing world.[5] Complications in the mother include obstructed labour, postpartum bleeding, eclampsia, and postpartum infection.[5] Complications in the baby include lack of oxygen at birth, birth trauma, and prematurity.[4][20]
The most prominent sign of labour is strong repetitive uterine contractions. Pain in contractions has been described as feeling similar to very strong menstrual cramps. Women giving birth are often encouraged to refrain from screaming.[citation needed] However, moaning and grunting may be encouraged to help lessen pain. Crowning may be experienced as an intense stretching and burning.
Back labour is a term for specific pain occurring in the lower back, just above the tailbone, during childbirth.[21]
Another prominent sign of labour is the rupture of membranes, commonly known as "water breaking". This is the leaking of fluid from the amniotic sac that surrounds a fetus in the uterus and helps provide cushion and thermoregulation. However, it is common for water to break long before contractions begin and in which case it is not a sign of immediate labour and hospitalization is generally required for monitoring the fetus and prevention of preterm birth.
During the later stages of gestation there is an increase in abundance of oxytocin, a hormone that is known to evoke feelings of contentment, reductions in anxiety, and feelings of calmness and security around the mate.[22] Oxytocin is further released during labour when the fetus stimulates the cervix and vagina, and it is believed that it plays a major role in the bonding of a mother to her infant and in the establishment of maternal behavior. The act of nursing a child also causes a release of oxytocin to help the baby get milk more easily from the nipple.[23]
Station refers to the relationship of the fetal presenting part to the level of the ischial spines. When the presenting part is at the ischial spines the station is 0 (synonymous with engagement). If the presenting fetal part is above the spines, the distance is measured and described as minus stations, which range from 1 to 4cm. If the presenting part is below the ischial spines, the distance is stated as plus stations ( +1 to +4cm). At +3 and +4 the presenting part is at the perineum and can be seen.[24]
The fetal head may temporarily change shape (becoming more elongated or cone shaped) as it moves through the birth canal. This change in the shape of the fetal head is called molding and is much more prominent in women having their first vaginal delivery.[25]
Cervical ripening is the physical and chemical changes in the cervix to prepare it for the stretching that will take place as the fetus moves out of the uterus and into the birth canal. A scoring system called a Bishop score can be used to judge the degree of cervical ripening in order to predict the timing of labour and delivery of the infant or for women at risk for preterm labour. It is also used to judge when a woman will respond to induction of labour for a postdate pregnancy or other medical reasons. There are several methods of inducing cervical ripening which will allow the uterine contractions to effectively dilate the cervix.[26]
Vaginal delivery involves four stages of labour: the shortening and opening of the cervix during the first stage, descent and birth of the baby during the second, the delivery of the placenta during the third, and the 4th stage of recovery which lasts until two hours after the delivery. The first stage is characterized by abdominal cramping or back pain that typically lasts around half a minute and occurs every 10 to 30 minutes.[13] The contractions (and pain) gradually becomes stronger and closer together.[14] The second stage ends when the infant is fully expelled. In the third stage, the delivery of the placenta.[15] The fourth stage of labour involves recovery, the uterus beginning to contract to pre-pregnancy state, delayed clamping of the umbilical cord, and monitoring of the neonatal tone and vitals.[16] As of 2014,[update] all major health organizations advise that immediately following a live birth, regardless of the delivery method, that the infant be placed on the mother's chest, termed skin-to-skin contact, and delaying routine procedures for at least one to two hours or until the baby has had its first breastfeeding.[17][18][19]
Definitions of the onset of labour include:
Many women are known to experience what has been termed the "nesting instinct". Women report a spurt of energy shortly before going into labour.[30] Common signs that labour is about to begin may include what is known as lightening, which is the process of the baby moving down from the rib cage with the head of the baby engaging deep in the pelvis. The pregnant woman may then find breathing easier, since her lungs have more room for expansion, but pressure on her bladder may cause more frequent need to void (urinate). Lightening may occur a few weeks or a few hours before labour begins, or even not until labour has begun.[30] Some women also experience an increase in vaginal discharge several days before labour begins when the "mucus plug", a thick plug of mucus that blocks the opening to the uterus, is pushed out into the vagina. The mucus plug may become dislodged days before labour begins or not until the start of labour.[30]
While inside the uterus the baby is enclosed in a fluid-filled membrane called the amniotic sac. Shortly before, at the beginning of, or during labour the sac ruptures. Once the sac ruptures, termed "the water breaks", the baby is at risk for infection and the mother's medical team will assess the need to induce labour if it has not started within the time they believe to be safe for the infant.[30]
The first stage of labour is divided into latent and active phases, where the latent phase is sometimes included in the definition of labour,[31] and sometimes not.[32]
The latent phase is generally defined as beginning at the point at which the woman perceives regular uterine contractions.[33] In contrast, Braxton Hicks contractions, which are contractions that may start around 26 weeks gestation and are sometimes called "false labour", are infrequent, irregular, and involve only mild cramping.[34]
Cervical effacement, which is the thinning and stretching of the cervix, and cervical dilation occur during the closing weeks of pregnancy. Effacement is usually complete or near-complete and dilation is about 5cm by the end of the latent phase.[35] The degree of cervical effacement and dilation may be felt during a vaginal examination.
The active phase of labour has geographically differing definitions. The World Health Organization describes the active first stage as "a period of time characterized by regular painful uterine contractions, a substantial degree of cervical effacement and more rapid cervical dilatation from 5 cm until full dilatation for first and subsequent labours.[36] In the US, the definition of active labour was changed from 3 to 4cm, to 5cm of cervical dilation for multiparous women, mothers who had given birth previously, and at 6cm for nulliparous women, those who had not given birth before.[37] This was done in an effort to increase the rates of vaginal delivery.[38]
Health care providers may assess the mother's progress in labour by performing a cervical exam to evaluate the cervical dilation, effacement, and station. These factors form the Bishop score. The Bishop score can also be used as a means to predict the success of an induction of labour.
During effacement, the cervix becomes incorporated into the lower segment of the uterus. During a contraction, uterine muscles contract causing shortening of the upper segment and drawing upwards of the lower segment, in a gradual expulsive motion.[39] The presenting fetal part then is permitted to descend. Full dilation is reached when the cervix has widened enough to allow passage of the baby's head, around 10cm dilation for a term baby.
A standard duration of the latent first stage has not been established and can vary widely from one woman to another. However, the duration of active first stage (from 5 cm until full cervical dilatation) usually does not extend beyond 12 hours in the first labour("primiparae"), and usually does not extend beyond 10 hours in subsequent labours ("multiparae").[40]
Dystocia of labour, also called "dysfunctional labour" or "failure to progress", is difficult labour or abnormally slow progress of labour, involving progressive cervical dilatation or lack of descent of the fetus. Friedman's Curve, developed in 1955, was for many years used to determine labour dystocia. However, more recent medical research suggests that the Friedman curve may not be currently[when?] applicable.[41][42]
The expulsion stage begins when the cervix is fully dilated, and ends when the baby is born. As pressure on the cervix increases, a sensation of pelvic pressure is experienced, and, with it, an urge to begin pushing. At the beginning of the normal second stage, the head is fully engaged in the pelvis; the widest diameter of the head has passed below the level of the pelvic inlet. The fetal head then continues descent into the pelvis, below the pubic arch and out through the vaginal opening. This is assisted by the additional maternal efforts of pushing, or bearing down, similar to defecation. The appearance of the fetal head at the vaginal opening is termed crowning. At this point, the mother will feel an intense burning or stinging sensation.
When the amniotic sac has not ruptured during labour or pushing, the infant can be born with the membranes intact. This is referred to as "delivery en caul".
Complete expulsion of the baby signals the successful completion of the second stage of labour. Some babies, especially preterm infants, are born covered with a waxy or cheese-like white substance called vernix. It is thought to have some protective roles during fetal development and for a few hours after birth.
The second stage varies from one woman to another. In first labours, birth is usually completed within three hours whereas in subsequentlabours, birth is usually completed within two hours.[43] Second-stage labours longer than three hours are associated with declining rates of spontaneous vaginal delivery and increasing rates of infection, perineal tears, and obstetric haemorrhage, as well as the need for intensive care of the neonate.[44]
The period from just after the fetus is expelled until just after the placenta is expelled is called the third stage of labour or the involution stage. Placental expulsion begins as a physiological separation from the wall of the uterus. The average time from delivery of the baby until complete expulsion of the placenta is estimated to be 1012 minutes dependent on whether active or expectant management is employed.[45] In as many as 3% of all vaginal deliveries, the duration of the third stage is longer than 30 minutes and raises concern for retained placenta.[46]
Placental expulsion can be managed actively or it can be managed expectantly, allowing the placenta to be expelled without medical assistance. Active management is the administration of a uterotonic drug within one minute of fetal delivery, controlled traction of the umbilical cord and fundal massage after delivery of the placenta, followed by performance of uterine massage every 15 minutes for two hours.[47] In a joint statement, World Health Organization, the International Federation of Gynaecology and Obstetrics and the International Confederation of Midwives recommend active management of the third stage of labour in all vaginal deliveries to help to prevent postpartum haemorrhage.[48][49][50]
Delaying the clamping of the umbilical cord for at least one minute or until it ceases to pulsate, which may take several minutes, improves outcomes as long as there is the ability to treat jaundice if it occurs. For many years it was believed that late cord cutting led to a mother's risk of experiencing significant bleeding after giving birth, called postpartum bleeding. However a recent review found that delayed cord cutting in healthy full-term infants resulted in early haemoglobin concentration and higher birthweight and increased iron reserves up to six months after birth with no change in the rate of postpartum bleeding.[51][52]
The fourth stage of labour is the period beginning immediately after childbirth, and extends for about six weeks. The terms postpartum and postnatal are often used for this period.[53] The woman's body, including hormone levels and uterus size, return to a non-pregnant state and the newborn adjusts to life outside the mother's body. The World Health Organization (WHO) describes the postnatal period as the most critical and yet the most neglected phase in the lives of mothers and babies; most deaths occur during the postnatal period.[54]
Following the birth, if the mother had an episiotomy or a tearing of the perineum, it is stitched. This is also an optimal time for uptake of long-acting reversible contraception (LARC), such as the contraceptive implant or intrauterine device (IUD), both of which can be inserted immediately after delivery while the woman is still in the delivery room.[55][56] The mother has regular assessments for uterine contraction and fundal height,[57] vaginal bleeding, heart rate and blood pressure, and temperature, for the first 24 hours after birth. Some women may experience an uncontrolled episode of shivering or postpartum chills following the birth. The first passing of urine should be documented within six hours.[54] Afterpains (pains similar to menstrual cramps), contractions of the uterus to prevent excessive blood flow, continue for several days. Vaginal discharge, termed "lochia", can be expected to continue for several weeks; initially bright red, it gradually becomes pink, changing to brown, and finally to yellow or white.[58]
At one time babies born in hospitals were removed from their mothers shortly after birth and brought to the mother only at feeding times.[59] Mothers were told that their newborn would be safer in the nursery and that the separation would offer the mother more time to rest. As attitudes began to change, some hospitals offered a "rooming in" option wherein after a period of routine hospital procedures and observation, the infant could be allowed to share the mother's room. As of 2020, rooming in has increasingly become standard practice in maternity wards.[60]
Humans are bipedal with an erect stance. The erect posture causes the weight of the abdominal contents to thrust on the pelvic floor, a complex structure which must not only support this weight but allow, in women, three channels to pass through it: the urethra, the vagina and the rectum. The infant's head and shoulders must go through a specific sequence of maneuvers in order to pass through the ring of the mother's pelvis. Range of motion and ambulation are typically unaffected during labour and it is encouraged that the mother move to help facilitate progression of labour. The vagina is called a 'birth canal' when the baby enters this passage. Six phases of a typical vertex or cephalic (head-first presentation) delivery:
Failure to complete the cardinal movements of birth in the correct order may result in complications of labour and birth injuries.
Skin-to-skin contact (SSC), sometimes also called kangaroo care, is a technique of newborn care where babies are kept chest-to-chest and skin-to-skin with a parent, typically their mother, though more recently (2022) their father as well. This means without the shirt or undergarments on the chest of both the baby and parent. A 2011 medical review found that early skin-to-skin contact resulted in a decrease in infant crying, improved cardio-respiratory stability and blood glucose levels, and improved breastfeeding duration.[61][62] A 2016 Cochrane review also found that SSC at birth promotes the likelihood and effectiveness of breastfeeding.[63]
As of 2014, early postpartum SSC is endorsed by all major organizations that are responsible for the well-being of infants, including the American Academy of Pediatrics.[17] The World Health Organization (WHO) states that "the process ofchildbirth is not finished until the baby has safely transferred from placental to mammary nutrition." It is advised that the newborn be placed skin-to-skin with the mother following vaginal birth, or as soon as the mother is alert and responsive after a Caesarean section, postponing any routine procedures for at least one to two hours. The baby's father or other support person may also choose to hold the baby SSC until the mother recovers from the anesthetic.[64]
The WHO suggests that any initial observations of the infant can be done while the infant remains close to the mother, saying that even a brief separation before the baby has had its first feed can disturb the bonding process. They further advise frequent skin-to-skin contact as much as possible during the first days after delivery, especially if it was interrupted for some reason after the delivery.[18][19]
La Leche League advises women to have a delivery team which includes a support person who will advocate to assure that:
It has long been known that a mother's level of the hormone oxytocin elevates in a mother when she interacts with her infant. In 2019, a large review of the effects of oxytocin found that the oxytocin level in fathers that engage in SSC is increased as well. Two studies found that "when the infant is clothed only in a diaper and placed in between the mother or father's breasts, chest-to-chest [elevated paternal oxytocin levels were] shown to reduce stress and anxiety in parents after interaction."[66]
For births that occur in hospitals the WHO recommends a hospital stay of at least 24 hours following an uncomplicated vaginal delivery and 96 hours for a Cesarean section. Looking at length of stay (in 2016) for an uncomplicated delivery around the world shows an average of less that 1 day in Egypt to 6 days in (pre-war) Ukraine. Averages for Australia are 2.8 days and 1.5 days in the UK.[67] While this number is low, two-thirds of women in the UK have midwife-assisted births and in some cases the mother may choose a hospital setting for birth to be closer to the wide range of assistance available for an emergency situation. However, women with midwife care may leave the hospital shortly after birth and her midwife will continue her care at her home.[68]In the U.S. the average length of stay has gradually dropped from 4.1 days in 1970 to a current stay of 2 days. The CDC attributed the drop to the rise in health care costs, saying people could not afford to stay in the hospital any longer. To keep it from dropping any lower, in 1996 congress passed the Newborns' and Mothers' Health Protection Act that requires insurers to cover at least 48 hours for uncomplicated delivery.[67]
In many cases and with increasing frequency, childbirth is achieved through labour induction or caesarean section. Labour induction is the process or treatment that stimulates childbirth and delivery. Inducing labour can be accomplished with pharmaceutical or non-pharmaceutical methods. Inductions are most often performed either with prostaglandin drug treatment alone, or with a combination of prostaglandin and intravenous oxytocin treatment.[69]Caesarean section is the removal of the neonate through a surgical incision in the abdomen, rather than through vaginal birth.[70] Childbirth by C-sections increased 50% in the US from 1996 to 2006. In 2012, about 23 million deliveries occurred by Caesarean section.[71][14] Induced births and elective cesarean before 39 weeks can be harmful to the neonate as well as harmful or without benefit to the mother. Therefore, many guidelines recommend against non-medically required induced births and elective cesarean before 39 weeks.[72] The 2012 rate of labour induction in the United States was 23.3 per cent, and had more than doubled from 1990 to 2010.[73][74]The American Congress of Obstetricians and Gynecologists (ACOG) guidelines recommend a full evaluation of the maternal-fetal status, the status of the cervix, and at least a 39 completed weeks (full term) of gestation for optimal health of the newborn when considering elective induction of labour. Per these guidelines, indications for induction may include:
Induction is also considered for logistical reasons, such as the distance from hospital or psychosocial conditions, but in these instances gestational age confirmation must be done, and the maturity of the fetal lung must be confirmed by testing. The ACOG also note that contraindications for induced labour are the same as for spontaneous vaginal delivery, including vasa previa, complete placenta praevia, umbilical cord prolapse or active genital herpes simplex infection.[75]
A Caesarean section, also called a C section, can be the safest option for delivery in some pregnancies. During a C section, the patient is usually numbed with an epidural or a spinal block, but general anesthesia can be used as well. A cut is made in the patients abdomen and then in the uterus to remove the baby. A C section may be the best option when the small size or shape of the mother's pelvis makes delivery of the baby impossible, or the lie or presentation of the baby as it prepares to enter the birth canal is dangerous. Other medical reasons for C section are placenta previa (the placenta blocks the babys path to the birth canal), uterine rupture, or fetal distress, like due to endangerment of the babys oxygen supply.[76] Before the 1970s, once a patient delivered one baby via C section, it was recommended that all of her future babies be delivered by C section, but that recommendation has changed. Unless there is some other indication, mothers can attempt a trial of labour and most are able to have a vaginal birth after C section (VBAC).[77]
Like any procedure, a C section is not without risks. Having a C section puts the mother at greater risk for uterine rupture and abnormal attachment of the placenta to the uterus in future pregnancies (placenta accreta spectrum).[78] The rate of deliveries occurring via C section instead of vaginal deliveries has been increasing since the 1970s. The WHO recommends a C section rate of between 10 to 15 percent because C sections rates higher than 10 percent are not associated with a decrease in morbidity and mortality.[79]
Obstetric care frequently subjects women to institutional routines, which may have adverse effects on the progress of labour. Supportive care during labour may involve emotional support, comfort measures, and information and advocacy which may promote the physical process of labour as well as women's feelings of control and competence, thus reducing the need for obstetric intervention. The continuous support may be provided either by hospital staff such as nurses or midwives, doulas, or by companions of the woman's choice from her social network.There is increasing evidence to show that the participation of the child's father in the birth leads to a better birth and also post-birth outcomes, providing the father does not exhibit excessive anxiety.[81]
Continuous labour support may help women to give birth spontaneously, that is, without caesarean or vacuum or forceps, with slightly shorter labours, and to have more positive feelings regarding their experience of giving birth. Continuous labour support may also reduce women's use of pain medication during labour and reduce the risk of babies having low five-minute Agpar scores.[82]
Eating or drinking during labour is an area of ongoing debate. While some have argued that eating in labour has no harmful effects on outcomes,[83] others continue to have concern regarding the increased possibility of an aspiration event (choking on recently eaten foods) in the event of an emergency delivery due to the increased relaxation of the oesophagus in pregnancy, upward pressure of the uterus on the stomach, and the possibility of general anaesthetic in the event of an emergency cesarean.[84] A 2013 Cochrane review found that with good obstetrical anaesthesia there is no change in harms from allowing eating and drinking during labour in those who are unlikely to need surgery. They additionally acknowledge that not eating does not mean there is an empty stomach or that its contents are not as acidic. They therefore conclude that "women should be free to eat and drink in labour, or not, as they wish."[85]
At one time shaving of the area around the vagina, was common practice due to the belief that hair removal reduced the risk of infection, made an episiotomy (a surgical cut to enlarge the vaginal entrance) easier, and helped with instrumental deliveries. It is currently less common, though it is still a routine procedure in some countries even though a systematic review found no evidence to recommend shaving.[86] Side effects appear later, including irritation, redness, and multiple superficial scratches from the razor. Another effort to prevent infection has been the use of the antiseptic chlorhexidine or providone-iodine solution in the vagina. Evidence of benefit with chlorhexidine is lacking.[87] A decreased risk is found with providone-iodine when a cesarean section is to be performed.[88]
An assisted delivery is used in about 1 in 8 births, and may be needed if either mother or infant appears to be at risk during a vaginal delivery. The methods used are termed obstetrical forceps extraction and vacuum extraction, also called ventouse extraction. Done properly, they are both safe with some preference for forceps rather than vacuum, and both are seen as preferable to an unexpected C-section. While considered safe, some risks for the mother include vaginal tearing, including a higher chance of having a more major vaginal tear that involves the muscle or wall of the anus or rectum. For women undergoing operative vaginal delivery with vacuum extraction or forceps, there is strong evidence that prophylactic antibiotics help to reduce the risk of infection.[89] There is a higher risk of blood clots forming in the legs or pelvis anti-clot stockings or medication may be ordered to avoid clots. Urinary incontinence is not unusual after childbirth but it is more common after an instrument delivery. Certain exercises and physiotherapy will help the condition to improve.[90]
Some women prefer to avoid analgesic medication during childbirth. Psychological preparation may be beneficial. Relaxation techniques, immersion in water, massage, and acupuncture may provide pain relief. Acupuncture and relaxation were found to decrease the number of caesarean sections required.[91] Immersion in water has been found to relieve pain during the first stage of labour and to reduce the need for anaesthesia and shorten the duration of labour, however the safety and efficacy of immersion during birth, water birth, has not been established or associated with maternal or fetal benefit.[92]
Most women like to have someone to support them during labour and birth; such as a midwife, nurse, or doula; or a lay person such as the father of the baby, a family member, or a close friend. Studies have found that continuous support during labour and delivery reduce the need for medication and a caesarean or operative vaginal delivery, and result in an improved Apgar score for the infant.[93][94]
Different measures for pain control have varying degrees of success and side effects to the woman and her baby. In some countries of Europe, doctors commonly prescribe inhaled nitrous oxide gas for pain control, especially as 53% nitrous oxide, 47% oxygen, known as Entonox; in the UK, midwives may use this gas without a doctor's prescription.[95] Opioids such as fentanyl may be used, but if given too close to birth there is a risk of respiratory depression in the infant.[needs update][96]
Popular medical pain control in hospitals include the regional anaesthetics epidurals (EDA), and spinal anaesthesia. Epidural analgesia is a generally safe and effective method of relieving pain in labour, but has been associated with longer labour, more operative intervention (particularly instrument delivery), and increases in cost.[97] However, a more recent (2017) Cochrane review suggests that the new epidural techniques have no effect on labour time and the use of instruments or the need for C-section deliveries.[98] Generally, pain and stress hormones rise throughout labour for women without epidurals, while pain, fear, and stress hormones decrease upon administration of epidural analgesia, but rise again later.[99]Medicine administered via epidural can cross the placenta and enter the bloodstream of the fetus.[100] Epidural analgesia has no statistically significant impact on the risk of caesarean section, and does not appear to have an immediate effect on neonatal status as determined by Apgar scores.[98]
Augmentation is the process of stimulating the uterus to increase the intensity and duration of contractions after labour has begun. Several methods of augmentation are commonly been used to treat slow progress of labour (dystocia) when uterine contractions are assessed to be too weak. Oxytocin is the most common method used to increase the rate of vaginal delivery.[101] The World Health Organization recommends its use either alone or with amniotomy (rupture of the amniotic membrane) but advises that it must be used only after it has been correctly confirmed that labour is not proceeding properly if harm is to be avoided. The WHO does not recommend the use of antispasmodic agents for prevention of delay in labour.[102]
For years an episiotomy was thought to help prevent more extensive vaginal tears and heal better than a natural tear. Perineal tears can occur at the vaginal opening as the baby's head passes through, especially if the baby descends quickly. Tears can involve the perineal skin or extend to the muscles and the anal sphincter and anus. Once common, they are now recognised as generally not needed.[14] When needed, the midwife or obstetrician makes a surgical cut in the perineum to prevent severe tears that can be difficult to repair. A 2017 Cochrane review compared episiotomy as needed (restrictive) with routine episiotomy to determine the possible benefits and harms for mother and baby. The review found that restrictive episiotomy policies appeared to give a number of benefits compared with using routine episiotomy. Women experienced less severe perineal trauma, less posterior perineal trauma, less suturing and fewer healing complications at seven days with no difference in occurrence of pain, urinary incontinence, painful sex or severe vaginal/perineal trauma after birth.[103]
In cases of a head first-presenting first twin, twins can often be delivered vaginally. In some cases twin delivery is done in a larger delivery room or in an operating theatre, in the event of complication e.g.
For external monitoring of the fetus during childbirth, a simple pinard stethoscope or doppler fetal monitor ("doptone") can be used.A method of external (noninvasive) fetal monitoring (EFM) during childbirth is cardiotocography (CTG), using a cardiotocograph that consists of two sensors: The heart (cardio) sensor is an ultrasonic sensor, similar to a Doppler fetal monitor, that continuously emits ultrasound and detects motion of the fetal heart by the characteristic of the reflected sound. The pressure-sensitive contraction transducer, called a tocodynamometer (toco) has a flat area that is fixated to the skin by a band around the belly. The pressure required to flatten a section of the wall correlates with the internal pressure, thereby providing an estimate of contraction.[104]Monitoring with a cardiotocograph can either be intermittent or continuous.[105] The World Health Organization (WHO) advises that for healthy women undergoing spontaneous labour continuous cardiotocography is not recommended for assessment of fetal well-being. The WHO states: "In countries and settings where continuous CTG is used defensively to protect against litigation, all stakeholders should be made aware that this practice is not evidence-based and does not improve birth outcomes."[106]
A mother's water has to break before internal (invasive) monitoring can be used. More invasive monitoring can involve a fetal scalp electrode to give an additional measure of fetal heart activity, and/or intrauterine pressure catheter (IUPC). It can also involve fetal scalp pH testing.[medical citation needed]
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Per figures retrieved in 2015, since 1990 there has been a 44 per cent decline in the maternal death rate. However, according to 2015 figures 830 women die every day from causes related to pregnancy or childbirth and for every woman who dies, 20 or 30 encounter injuries, infections or disabilities. Most of these deaths and injuries are preventable.[108][109]
In 2008, noting that each year more than 100,000 women die of complications of pregnancy and childbirth and at least seven million experience serious health problems while 50 million more have adverse health consequences after childbirth, the World Health Organization (WHO) has urged midwife training to strengthen maternal and newborn health services. To support the upgrading of midwifery skills the WHO established a midwife training program, Action for Safe Motherhood.[5]
The rising maternal death rate in the US is of concern. In 1990 the US ranked 12th of the 14 developed countries that were analysed. However, since that time the rates of every country have steadily continued to improve while the US rate has spiked dramatically. While every other developed nation of the 14 analysed in 1990 shows a 2017 death rate of less than 10 deaths per every 100,000 live births, the US rate has risen to 26.4. By comparison, the United Kingdom ranks second highest at 9.2 and Finland is the safest at 3.8.[110] Furthermore, for every one of the 700 to 900 US woman who die each year during pregnancy or childbirth, 70 experience significant complications such as haemorrhage and organ failure, totalling more than one per cent of all births.[111]
Compared to other developed nations, the United States also has high infant mortality rates. The Trust for America's Health reports that as of 2011, about one-third of American births have some complications; many are directly related to the mother's health including increasing rates of obesity, type 2 diabetes, and physical inactivity. The U.S. Centers for Disease Control and Prevention (CDC) has led an initiative to improve woman's health previous to conception in an effort to improve both neonatal and maternal death rates.[112]
The second stage of labour may be delayed or lengthy due to poor or uncoordinated uterine action, an abnormal uterine position such as breech or shoulder dystocia, and cephalopelvic disproportion (a small pelvis or large infant). Prolonged labour may result in maternal exhaustion, fetal distress, and other complications including obstetric fistula.[113]
Eclampsia is the onset of seizures (convulsions) in a woman with pre-eclampsia. Pre-eclampsia is a disorder of pregnancy in which there is high blood pressure and either large amounts of protein in the urine or other organ dysfunction. Pre-eclampsia is routinely screened for during prenatal care. Onset may be before, during, or rarely, after delivery. Around one per cent of women with eclampsia die.[medical citation needed]
A puerperal disorder or postpartum disorder is a complication which presents primarily during the puerperium, or postpartum period. The postpartum period can be divided into three distinct stages; the initial or acute phase, six to 12 hours after childbirth; subacute postpartum period, which lasts two to six weeks, and the delayed postpartum period, which can last up to six months. In the subacute postpartum period, 87% to 94% of women report at least one health problem.[114][115] Long-term health problems (persisting after the delayed postpartum period) are reported by 31 per cent of women.[116]
According to the WHO, hemorrhage is the leading cause of maternal death worldwide accounting for approximately 27.1% of maternal deaths.[117] Within maternal deaths due to hemorrhage, two-thirds are caused by postpartum hemorrhage.[117] The causes of postpartum hemorrhage can be separated into four main categories: Tone, Trauma, Tissue, and Thrombin. Tone represents uterine atony, the failure of the uterus to contract adequately following delivery. Trauma includes lacerations or uterine rupture. Tissue includes conditions that can lead to a retained placenta. Thrombin, which is a molecule used in the human bodys blood clotting system, represents all coagulopathies.[118]
Postpartum infections, also historically known as childbed fever and medically as puerperal fever, are any bacterial infections of the reproductive tract following childbirth or miscarriage. Signs and symptoms usually include a fever greater than 38.0C (100.4F), chills, lower abdominal pain, and possibly bad-smelling vaginal discharge. The infection usually occurs after the first 24 hours and within the first ten days following delivery. Infection remains a major cause of maternal deaths and morbidity in the developing world. The work of Ignaz Semmelweis was seminal in the pathophysiology and treatment of childbed fever and his work saved many lives.[119]
Childbirth can be an intense event and strong emotions, both positive and negative, can be brought to the surface. Abnormal and persistent fear of childbirth is known as tokophobia. The prevalence of fear of childbirth around the world ranges between 425%, with 37% of pregnant women having clinical fear of childbirth.[120][121]
Most new mothers may experience mild feelings of unhappiness and worry after giving birth. Babies require a lot of care, so it is normal for mothers to be worried about, or tired from, providing that care. The feelings, often termed the "baby blues", affect up to 80 per cent of mothers. They are somewhat mild, last a week or two, and usually go away on their own.[122]
Postpartum depression is different from the "baby blues". With postpartum depression, feelings of sadness and anxiety can be extreme and might interfere with a woman's ability to care for herself or her family. Because of the severity of the symptoms, postpartum depression usually requires treatment. The condition, which occurs in nearly 15 percent of births, may begin shortly before or any time after childbirth, but commonly begins between a week and a month after delivery.[122]
Childbirth-related posttraumatic stress disorder is a psychological disorder that can develop in women who have recently given birth.[123][124][125] Causes include issues such as an emergency C-section, preterm labour, inadequate care during labour,lack of social support following childbirth, and others. Examples of symptoms include intrusive symptoms, flashbacks and nightmares, as well as symptoms of avoidance (including amnesia for the whole or parts of the event), problems in developing a mother-child attachment, and others similar to those commonly experienced in posttraumatic stress disorder (PTSD). Many women who are experiencing symptoms of PTSD after childbirth are misdiagnosed with postpartum depression or adjustment disorders. These diagnoses can lead to inadequate treatment.[126]
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Unlocking the Mysteries of Brain Regeneration Groundbreaking Study Offers New Insight – SciTechDaily
Neuron generation trajectories. Credit: BGI Genomics
Because of its distinctive and adorable look, the axolotl Ambystoma mexicanum is a popular pet. Unlike other metamorphosing salamanders, axolotls (pronounced ACK-suh-LAH-tuhl) never outgrow their larval, juvenile stage, a trait known as neoteny. Its also recognized for its ability to regenerate missing limbs and other tissues including the brain, spinal cord, tail, skin, limbs, liver, skeletal muscle, heart, upper and lower jaw, and ocular tissues like the retina, cornea, and lens.
Mammals, including humans, are almost incapable of rebuilding damaged tissue after a brain injury. Some species, such as fish and axolotls, on the other hand, may replenish wounded brain regions with new neurons.
Tissue types the axolotl can regenerate as shown in red. Credit: Debuque and Godwin, 2016
Brain regeneration necessitates the coordination of complex responses in a time and region-specific way. In a paper published on the cover of Science, BGI and its research partners used Stereo-seq technology to recreate the axolotl brain architecture throughout developing and regenerative processes at single-cell resolution. Examining the genes and cell types that enable axolotls to renew their brains might lead to better treatments for severe injuries and unlock human regeneration potential.
Cell regeneration images at seven different time points following an injury; the control image is on the left. Credit: BGI Genomics
The research team collected axolotl samples from six development stages and seven regeneration phases with corresponding spatiotemporal Stereo-seq data. The six developmental stages include:
Through the systematic study of cell types in various developmental stages, researchers found that during the early development stage neural stem cells located in the VZ region are difficult to distinguish between subtypes, and with specialized neural stem cell subtypes with spatial regional characteristics from adolescence, thus suggesting that various subtypes may have different functions during regeneration.
In the third part of the study, the researchers generated a group of spatial transcriptomic data of telencephalon sections that covered seven injury-induced regenerative stages. After 15 days, a new subtype of neural stem cells, reaEGC (reactive ependymoglial cells), appeared in the wound area.
Axolotl brain developmental and regeneration processes. Credit: BGI Genomics
Partial tissue connection appeared at the wound, and after 20 to 30 days, new tissue had been regenerated, but the cell type composition was significantly different from the non-injured tissue. The cell types and distribution in the damaged area did not return to the state of the non-injured tissue until 60 days post-injury.
The key neural stem cell subtype (reaEGC) involved in this process was derived from the activation and transformation of quiescent neural stem cell subtypes (wntEGC and sfrpEGC) near the wound after being stimulated by injury.
What are the similarities and differences between neuron formation during development and regeneration? Researchers discovered a similar pattern between development and regeneration, which is from neural stem cells to progenitor cells, subsequently into immature neurons and finally to mature neurons.
Spatial and temporal distribution of axolotl brain development. Credit: BGI Genomics
By comparing the molecular characteristics of the two processes, the researchers found that the neuron formation process is highly similar during regeneration and development, indicating that injury induces neural stem cells to transform themselves into a rejuvenated state of development to initiate the regeneration process.
Our team analyzed the important cell types in the process of axolotl brain regeneration, and tracked the changes in its spatial cell lineage, said Dr. Xiaoyu Wei, the first author of this paper and BGI-Research senior researcher. The spatiotemporal dynamics of key cell types revealed by Stereo-seq provide us a powerful tool to pave new research directions in life sciences.
Corresponding author Xun Xu, Director of Life Sciences at BGI-Research, noted that In nature, there are many self-regenerating species, and the mechanisms of regeneration are pretty diverse. With multi-omics methods, scientists around the world may work together more systematically.
Reference: Single-cell Stereo-seq reveals induced progenitor cells involved in axolotl brain regeneration by Xiaoyu Wei, Sulei Fu, Hanbo Li, Yang Liu, Shuai Wang, Weimin Feng, Yunzhi Yang, Xiawei Liu, Yan-Yun Zeng, Mengnan Cheng, Yiwei Lai, Xiaojie Qiu, Liang Wu, Nannan Zhang, Yujia Jiang, Jiangshan Xu, Xiaoshan Su, Cheng Peng, Lei Han, Wilson Pak-Kin Lou, Chuanyu Liu, Yue Yuan, Kailong Ma, Tao Yang, Xiangyu Pan, Shang Gao, Ao Chen, Miguel A. Esteban, Huanming Yang, Jian Wang, Guangyi Fan, Longqi Liu, Liang Chen, Xun Xu, Ji-Feng Fei and Ying Gu, 2 September 2022, Science.DOI: 10.1126/science.abp9444
This study has passed ethical reviews and follows the corresponding regulations and ethical guidelines.
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Unlocking the Mysteries of Brain Regeneration Groundbreaking Study Offers New Insight - SciTechDaily
TikTok Made Me Buy It: The Creamy Concealer That Instantly Veils Dark Circles and Hyperpigmentation – Vogue
Formulated as a rich cream, this product acts as a lightweight veil ideal for concealing, correcting, brightening, and contouring. Because of its texture, the Sweetener Concealer is especially a plus for dry-to-normal skin types craving added moisture in their makeup regimen. Whats more, as with other skincare-makeup hybrids, this has skin-nourishing ingredients at its corepacked with hyaluronic acid, vitamin E, raspberry stem cells, and ashwagandha for not only hydration, but protection against environmental stressors.
According to Thomas, a good pot concealer should offer a double pay-off, optimal coverage that acts as a foundation and concealer. She recommends applying under the eyes, around the nose, and on top of any spots or blemishes; blend with fingers, a sponge, or a brush.
For daily use, I prime with a hydrating mist and makeup primer. Then, I place a bit of the concealer on my skin, immediately buffing with a Beautyblender or complexion brush. Despite its rich texture, I find that it blends seamlessly, so I often wear it on its own instead of foundation for a skin-like finish, just as Thomas indicated. Because this leans towards full coverage, it instantly veils my dark spots and under-eye bags without any heavy layering.
Keep in mind, though, that this can crease easily on some skin types, so a good setting powder is essential for long-wear. My advice is to start with a small amount, building up to your desired coverage. A little goes a long way! Otherwise, this layers well with other products on top (think: cream blushes or Chanels bronzer) without feeling cakeyan ideal concealer for the cooler months ahead.
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TikTok Made Me Buy It: The Creamy Concealer That Instantly Veils Dark Circles and Hyperpigmentation - Vogue
Here Is Why You Heal Slower As You Age – Health Digest
You probably know what hormones are, and you may have at least heard about stem cells, but what is a growth factor? According to Britannica, it is a protein that stimulates growth in specific tissues. There are many types of growth factors, each with the job of repairing certain body parts. Some growth factors include epidermal growth factor (responsible for skin repair), platelet-derived growth factor (responsible for repairing muscles and connective tissues), and nerve growth factor (responsible for stimulating brain cell growth and repair).
According to a 2020 mini-review in Frontiers in Bioengineering and Biotechnology, growth factors are critical for tissue repair and regeneration. In short, growth factors help maintain skin health and heal wounds. As you age and fewer growth factors are available to help with repair and regeneration, injuries take longer to heal. Stem cells factor in because they release growth factors to instigate wound healing, according to a 2010 study in theInternational Journal of Stem Cells.
And the sex hormones estrogen and testosterone play a part in wound healing too. Low estrogen levels or high amounts of testosterone can slow healing. For women, estrogen levels drop after menopause, resulting in slowed healing time (via Wounds).
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Here Is Why You Heal Slower As You Age - Health Digest
A glimpse into Indian consumers expectations for cosmetic treatments and consumption insights – The Financial Express
By Dr Chytra V Anand
The fascination with beauty and skincare in India has grown leaps and bounds in recent times, and understandably so, given that the culture of beauty is deeply rooted in the country. The days when beauty was an aspect of social class and the cosmetic treatments and products you access gave away your economic status are long gone, as are the days when cosmetic treatments were considered a girl thing. With cosmetic treatments becoming more accessible and sought-after, the Indian skincare and derma cosmetics market generated an estimated revenue of a whopping USD 188.2 million in 2021. The same is projected to grow at a CAGR of 10.2% between 2021 and 2030.
Today, with changing lifestyles, demographic growth, cutting-edge technology, and improving economic and social conditions thanks to rising per capita and disposable income, India is quickly heading towards becoming a leader in the global cosmetics industry. But for a bit of self-introspection, what are Indian consumers looking for when it comes to cosmetic treatments? What does their consumption tell industry players?
Body hair removal has become one of the most popular cosmetic procedures done across the world today. But compared to shaving, waxing, or using an epilator or a trimmer, laser hair removal is a more permanent hair removal method that has gained immense traction of late. Especially in urban India, laser hair removal has quickly gained popularity, with mothers even bringing their 16-year-olds for Laser hair removal.
In 2021, the global laser hair removal market was valued atUSD 798.6 million, with an estimated CAGR of 18.4% from 2022 to 2030. Given that laser hair removal is a one-time procedure, although one has to sit through multiple sessions, the results, when done by a reliable cosmetic professional, are impressive. The Asia Pacific is projected to be the fastest-growing segment for laser hair removal, especially in countries like India and China.
A cosmetic procedure where a chemical solution is applied to your skin to remove the top layers, Chemical Peels ensure that the skin becomes smoother and clearer, making it radiant. On the other hand, a Medical Clean-up, in the simplest terms, is the procedure of cleaning your skin, ridding impurities like blackheads and white head spots to clear clogged pores. Besides, Medical Clean-ups are also beneficial for people struggling with acne scars, making it a popular procedure that an increasing number of people are choosing. For Chemical Peels, the market size is expected to touch USD 68.81 million between 2021 to 2025, making their popularity surge.
As we grow older, our skin begins to age too, and wrinkles and fine lines begin to appear on our face. Cosmetic procedures like Hydra Facials and skin maintenance with Laser Photofacials are a weekly must-do for 30-45-year-olds to ensure their skin is supple and glowing. Apart from this, the perception of Indian consumers when it comes to cosmetic treatments like Botox and Fillers has begun to change. These are no longer viewed as taboo as people now realise that they give your skin a lift.
Such treatments are also no longer only available for a certain section of society, like the wealthy. Botox and Fillers are now available to everyone, and consumers are looking at them from a skin maintenance standpoint rather than as a luxury, unnecessary treatment. Annually, the Botox segment is registering 20-25% growth in the country proof of evolving consumer preferences and the rising popularity of such treatments. Besides these, derma cosmetics and medical skin care have also gained a fair amount of traction, with skincare aficionados looking for effective and efficient skin care procedures that are non-surgical.
Alongside our skincare, taking care of our mane is equally important. For people struggling with hair fall, flaky and dry scalp, and other issues that affect your hair, stem cell therapy is the answer. Often done annually, stem cell therapy helps rejuvenate your hair cells to retain hair and repair damage. And with the global hair restoration market standing at over USD 4.2 billion in 2020, we can safely say its here to stay.
With consumerism changing face gradually and Indian consumers gaining access to world-class cosmetic treatments that are non-surgical, which still trump surgical procedures, the future of the Indian cosmetic treatments market shines bright. As long as the procedures are done by qualified and experienced professionals and are reliable and effective, the demand for such cosmetic procedures will continue to grow.
(The author isfounder ofKosmoderma Healthcare Pvt. Ltd.Views expressed are personal and do not reflect the official position or policy of the FinancialExpress.com.)
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A glimpse into Indian consumers expectations for cosmetic treatments and consumption insights - The Financial Express
Propanc Biopharma Targets Pancreatic & Ovarian Cancers for PRP Clinical Studies with Combined Markets to Reach Over $14.3 Billion by 2027 -…
MELBOURNE, Australia--(BUSINESS WIRE)--Propanc Biopharma, Inc. (OTC Pink: PPCB) (Propanc or the Company), a biopharmaceutical company developing novel cancer treatments for patients suffering from recurring and metastatic cancer, today announced that Chief Scientific Officer and Co-Founder, Dr Julian Kenyon, MD, MB, ChB, explains why pancreatic and ovarian cancers are selected as the primary target therapeutic indications for planned PRP human studies. According to Dr Kenyon, target indications were selected based on in vitro and in vivo data, as well as clinical observations from a compassionate use study investigating the effects of two proenzymes, trypsinogen and chymotrypsinogen against a range of malignant tumors. Overall, proenzymes appeared to exert significant effects against more aggressive, less differentiated tumor types, like pancreatic and ovarian tumors. Patients from the compassionate use study suffering from cancers of the GI tract, or endocrine tumors, such as pancreatic and ovarian cancers, benefited most from treatment. The world market for pancreatic and ovarian cancer drugs is projected to grow to $4.2 Billion in 2025 according to Grandview Research and $10.1 Billion by 2027 according to iHealthcareAnalyst, respectively, resulting in a combined global market of $14.3 Billion over the next 5-year period.
Extensive laboratory analysis confirmed that PRP reduced the main characteristics of cancer spread, namely angiogenesis (blood vessel formation), which is a critical step in tumor development, as well as the spreading of tumor metastases. In addition, assays revealed that the migration capacity of ovarian, pancreatic, melanoma and colon cancer cells was suppressed after incubation with PRP. Furthermore, evidence suggests the epithelial to mesenchymal transition (EMT), a biological process associated with wound healing and cell migration, which causes cancer stem cells (CSCs) to become motile and invasive, is associated with metastasis and inducing drug resistance in many cancers, such as pancreatic and ovarian cancers. Studies in pancreatic and cancer cell lines after PRP treatment demonstrated a significant reduction in EMT markers and genes and in fact, a reversal of the EMT process so that CSCs become benign and less resistant to standard treatments.
The in vivo effects of PRP at different doses on tumor weight in implanted pancreatic and ovary tumors was evaluated. In the pancreatic tumor model, there was significant reduction in mean tumor weight in animals treated for 26 days with PRP with more than 85% tumor growth inhibition compared with the control. Furthermore, ovary tumor-bearing mice showed a significant reduction in mean tumor weight in animals treated for 21 days with two different doses of PRP, resulting in a 46 52% tumor growth inhibition compared with the control.
The clinical efficacy of a suppository formulation containing bovine pancreatic proenzymes trypsinogen and chymotrypsinogen was evaluated in the context of a UK Pharmaceuticals Special Scheme and the results were published in Scientific Reports. Clinical effects were studied in 46 patients with advanced metastatic cancers of different origin (prostate, breast, ovarian, pancreatic, colorectal, stomach, non-small cell lung, bowel cancer and melanoma) after treatment with a rectal formulation of both pancreatic proenzymes. No severe or serious adverse events related to the rectal administration were observed. Patients did not experience any hematological side effects as typically seen with classical chemotherapy regimens.
In order to assess the therapeutic activity, overall survival of patients under treatment was compared to the life expectancy assigned to a patient prior to treatment start. Nineteen from 46 patients (41.3%) with advanced malignant diseases, most of them suffering from metastases, had a survival time significantly longer than their expected, in fact, for the whole set of cancer types, mean survival (9.0 months) was significantly higher than mean life expectancy (5.6 months). In the case of pancreatic and ovarian cancers, 2 from 4 pancreatic cancer patients and 4 from 7 ovarian cancer patients significantly exceeded life expectancy.
As a result of the extensive studies undertaken, particularly in pancreatic cancer, the Company applied for and received Orphan Drug Designation (ODD) from the US Food and Drug Administration (USFDA) for the use of its lead product, PRP, for the treatment of pancreatic cancer. The approved indication is one of the most lethal malignancies with a median survival of 6 months and a 5-year survival rate of less than 5%. The lethal nature of this disease stems from its propensity to rapidly disseminate to the lymphatic system and distant organs, and is a major unmet medical issue. Under the Orphan Drug Act (ODA), drugs, vaccines, and diagnostic agents qualify for orphan status if they are intended to treat a disease affecting less than 200,000 American citizens. Under the ODA, orphan drug sponsors qualify for seven-year FDA-administered market Orphan Drug Exclusivity (ODE), tax credits of up to 50% of R&D costs, R&D grants, waived FDA fees, protocol assistance and may get clinical trial tax incentives.
Over the past 15 years, our extensive research has uncovered a truly unique and exciting technology that selectively targets and eradicates cancer stem cells, whilst leaving healthy cells alone, making it less toxic compared with standard treatment approaches, said Dr Kenyon. Furthermore, our technology appears to be effective against more aggressive, less differentiated tumor types where few treatment options exist, and prognosis is poor, especially in the case of pancreatic and ovarian cancers. I look forward to advancing PRP to human studies where we can fully assess the clinical efficacy of PRP in a controlled setting.
Propanc plans to undertake a First-In-Human study in 30 to 40 advanced cancer patients suffering from solid tumors to determine a maximum tolerated dose for PRP treatment, followed by two proof of concept studies in pancreatic and ovarian cancers, 60 patients in each study, to confirm the clinical efficacy of PRP in the selected target therapeutic indications.
PRP is a mixture of two proenzymes, trypsinogen and chymotrypsinogen from bovine pancreas administered by intravenous injection. A synergistic ratio of 1:6 inhibits growth of most tumor cells. Examples include kidney, ovarian, breast, brain, prostate, colorectal, lung, liver, uterine and skin cancers.
About Propanc Biopharma, Inc.
Propanc Biopharma, Inc. (the Company) is developing a novel approach to prevent recurrence and metastasis of solid tumors by using pancreatic proenzymes that target and eradicate cancer stem cells in patients suffering from pancreatic, ovarian and colorectal cancers. For more information, please visit http://www.propanc.com.
The Companys novel proenzyme therapy is based on the science that enzymes stimulate biological reactions in the body, especially enzymes secreted by the pancreas. These pancreatic enzymes could represent the bodys primary defense against cancer.
To view the Companys Mechanism of Action video on its anti-cancer lead product candidate, PRP, please click on the following link: http://www.propanc.com/news-media/video
Forward-Looking Statements
All statements other than statements of historical facts contained in this press release are forward-looking statements, which may often, but not always, be identified by the use of such words as may, might, will, will likely result, would, should, estimate, plan, project, forecast, intend, expect, anticipate, believe, seek, continue, target or the negative of such terms or other similar expressions. These statements involve known and unknown risks, uncertainties and other factors, which may cause actual results, performance or achievements to differ materially from those expressed or implied by such statements. These factors include uncertainties as to the Companys ability to continue as a going concern absent new debt or equity financings; the Companys current reliance on substantial debt financing that it is unable to repay in cash; the Companys ability to successfully remediate material weaknesses in its internal controls; the Companys ability to reach research and development milestones as planned and within proposed budgets; the Companys ability to control costs; the Companys ability to obtain adequate new financing on reasonable terms; the Companys ability to successfully initiate and complete clinical trials and its ability to successful develop PRP, its lead product candidate; the Companys ability to obtain and maintain patent protection; the Companys ability to recruit employees and directors with accounting and finance expertise; the Companys dependence on third parties for services; the Companys dependence on key executives; the impact of government regulations, including FDA regulations; the impact of any future litigation; the availability of capital; changes in economic conditions, competition; and other risks, including, but not limited to, those described in the Companys periodic reports that are filed with the Securities and Exchange Commission and available on its website at http://www.sec.gov. These forward-looking statements speak only as of the date hereof and the Company disclaims any obligations to update these statements except as may be required by law.
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Propanc Biopharma Targets Pancreatic & Ovarian Cancers for PRP Clinical Studies with Combined Markets to Reach Over $14.3 Billion by 2027 -...