The new research showed that adult stem cells could help beat heart failure.

A sticking plaster made from adult stem cells could be a significant step towards combatting heart failure, scientists say.

Researchers discovered that stem cells taken from a patients thigh and transplanted onto the heart led to improved heart function after one year.

Heart failure is thought to affect between 500,000 to 900,000 people in the UK. It occurs when the heart becomes too weak to efficiently pump blood around the body.

The authors of the study, published in the Journal of the American Heart Association, said the therapy was potentially a long-term solution to the problem.

They said that, promising results in the safety and functional recovery warrant further clinical follow-up and larger studies, which they hope will confirm the treatments potential.

Professor Metin Avkiran, associate medical director at the British Heart Foundation, hailed the exciting breakthrough.

He said: Heart failure is a cruel and debilitating illness affecting more than half a million people across the UK. Currently, heart failure is incurable, but stem cell-based treatments may offer new hope to people suffering from the disease.

He echoed the call for further research, saying: The study involved only a small number of patients. In order to establish the long-term safety and benefits of the exciting new treatment we would need larger studies.

Heart failure often leaves sufferers struggling for breath and exhausted while carrying out simple everyday tasks, such as eating or getting dressed.

It can be caused by several issues including heart disease, diabetes and high blood pressure, but can also be the result of an unhealthy lifestyle.

Earlier this month, it was revealed that a remarkable new technique allows adult stem cells to be used to treat burn victims.

Taking a sample of skin stem cells and spraying them onto a victims burn caused new layers of skin to form over the burn, potentially healing even severe burns within weeks.

And in January, scientists released findings showing that synthetic cardiac stem cells could be used to treat patients who had suffered a heart attack by repairing the heart muscle damage.

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Stem cell 'plaster' could help heart failure patients - The Christian Institute

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In Brief Scientists from the University of Washington have constructed digital logic gates in living cells. Though they're not the first to do so, the researchers' living circuitry is the largest and most complex of any created thus far. Living Circuits

Thanks to projects like Elon Musks Neuralink, a future in which humankind merges with machinesis on everyones minds. While a brain computer interface (BCI) like the one Musk is proposing would involve making acomputer function as part ofa human body, other researchers are taking an opposite route. Instead of making machines that can imitate biology, theyre looking for ways to make biological systems function more like computers.

One such project is the topic of a study by researchers from the University of Washington (UW)that was justpublished inNature Communications. They have developed a new method of turning cells into computers that process information digitally instead of following their usual macromolecular processes. They did so by building cellular versions of logic gates commonly found in electric circuits.

The team built theirNOR gates, digital logic gates that pass a positive signal only when their two inputs are negative, in the DNA of yeast cells. Each of these cellular NOR gates was made up of three programmable DNA stretches, with two acting as inputs and one as an output. These specific DNA sequences were targeted using CRISPR-Cas9, with the Cas9 proteins serving as the molecular gatekeeper that determined if a certain gate shouldbe active or not.

This UW study isnt the first to buildcircuits in cells, but it is the most extensive one to date, with seven cellular NOR gates in a single eukaryotic cell. This added complexity puts us one step closer to transforming cells into biological computers witha number of potential medical applications.

While implementing simple programs in cells will never rival the speed or accuracy of computation in silicon, genetic programs can interact with the cells environment directly, senior author Eric Klavins explained in a press release. For example, reprogrammed cells in a patient could make targeted, therapeutic decisions in the most relevant tissues, obviating the need for complex diagnostics and broad spectrum approaches to treatment.

If given the ability to hackour biology in this way, we could potentially engineer immune cells to respond to cancer markers or cellular biosensors to diagnose infectious diseases. Essentially, wed have an effectiveway to fight diseases on the cellular level, ushering in a new era in human evolution.

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Scientists Are Using CRISPR To "Program" Living Cells - Futurism - Futurism

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CRISPR has built a tremendous amount of excitement in the scientific community since 2013. Though it can be used to create simple gene-disrupted animal models, it is extremely challenging to use it to insert foreign cassettes into genomes to create knock-ins or more complex models such as conditional knockouts.

A team headed by Dr. Channabasavaiah B Gurumurthy (Guru) at the University of Nebraska Medical Center, Omaha, U.S.A., in collaboration with Dr. Masato Ohtsuka, Tokai University, Japan have developed a method they call Easi-CRISPR.

This new technique revolutionizes the speed at which, much-needed, mutant mouse models are created for biomedical research.This work was published in Genome Biology journal on May 17, 2017.

TheEasi-CRISPR method employs long single stranded DNAs as donor cassettes for gene editing via CRISPR, unlike the typically very inefficient double stranded DNA donors commonly used by the scientific community. In addition, the ssDNA donors are combined with newer platforms of CRISPR guide RNAs (that constitute separated crRNA and tracrRNA) and Cas9 protein, together called ctRNP.

During the previous 4 years, many scientists have tried to use CRISPR to create knock-in models, that relied on homology-directed repair (HDR), but many were unsuccessful as their methods were not able to shift the balance from NHEJ to HDR for it to work efficiently. A recent Science Magazine news article captured the frustration of the research community about the limitations of the previously used CRISPR methods.

Gurus and Masatos labs first observed the robustness of ssDNA donors for HDR, in their Easi-CRISPR platform, in the summer of 2016. They posted their preliminary results on the preprint serverbiorXiv,started presenting their data at several conferences so that their method can immediately be available to the scientific community, before their manuscript was peer-reviewed and published in a journal.

Guru said Several independent labs have already been able to use Easi-CRISPR for other genes, thanks to its early online posting on bioRxiv.He added, Hundreds of labs are interested in using the technology we posted another bioRxiv article on this work today that describes detailed step-by-step protocols of Easi-CRISPR, which should help the community further.

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Fine-tuning CRISPR to Create Popular Mouse Models - Technology Networks

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XIANGTAN, Hunan, May 25, 2017 /PRNewswire/ -- Incidence of prostate cancer in China is on the rise, cells in the male prostate are overly replicating, creating cancerous growths that leave the patient in severe pain, constant feelings of urination, and a decrease in life expectancy if not treated. Current treatments for prostate cancer include invasive surgeries, radiation, and oral drugs, however, these western remedies often leave patients with adverse side effects (such as hair loss, nausea, weakness, and emotional damage). Medical researchers are now looking for new cancer treatment to treat prostate and other forms of cancer. The 3D prostate treatment based out of the 3D Urology and Prostate Clinic in China is taking this challenge with their research on gene therapy and how genes created can be transferred to the target region. Gene therapy allows for certain genes to be turned on/off creating an enzymatic cascade that can lead to different outcomes, in cancer researchers hope that gene therapy can stop cell growth and induce apoptosis of tumor cells.

Scientists have created novel "suicide genes" that induce apoptosis in vivo. The human body is more complex than test organisms so getting genes to the right location requires a lot of work, simply swallowing a pill will have the suicides genes be destroyed by hydrochloric acid and digestive enzymes in the stomach. To mediate this issue medical researchers are now using injections of suicide genes coupled to vectors. Current day vectors for gene therapy are done through viruses that are tacked with the lab created genes, however, this process leaves patients susceptible to attacks by the virus. Dr. Xinping Song's 3D prostate clinic has been exploring alternative and more natural methods for gene therapy transfer. Vectors investigated by the Dr. Xinping Song include nanoparticles and cationic liposomes, chitosan, and alkaline polysaccharides, their findings showed that these vectors were all highly specific to cancerous tumors and help get the genes to undergo apoptosis into the tumor cells.

Medical research must continue to experiment with different genes and vectors to push to cure prostate and other forms of cancer. Gene therapy can treat certain forms of cancer naturally with no side effects.

Contact:

Alisa Wang

86-186-7321-6429

prostatecure3d(at)gmail(dot)com

To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/dr-xinping-songs-3d-prostate-treatment-investigates-vectors-for-gene-therapy-in-prostate-cancer-300463869.html

SOURCE Dr. Song's 3D Prostate and 3D Prostatitis Clinic

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Dr. Xinping Song's 3D Prostate Treatment Investigates Vectors for ... - PR Newswire (press release)

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Stem cell researchers at the University of Calgary have found another piece of the puzzle behind what may contribute to hair loss and prevent wounds from healing normally.

Jeff Biernaskies research, published recently in the scientific journal npj Regenerative Medicine identifies a key signalling protein called platelet-derived growth factor (PDGF). This protein is critical for driving self-renewal and proliferation of dermal stem cells that live in hair follicles and enable their unique ability to continuously regenerate and produce new hair.

This is the first study to identify the signals that influence hair follicle dermal stem cell function in your skin, says Biernaskie, an associate professor in comparative biology and experimental medicine at the University of Calgary's Faculty of Veterinary Medicine, and Calgary Firefighters Burn Treatment Society Chair in Skin Regeneration and Wound Healing. Biernaskie is also a member of the Alberta Childrens Hospital Research Institute.

What we show is that in the absence of PDGF signalling hair follicle dermal stem cells are rapidly diminished because of their inability to generate new stem cells and produce sufficient numbers of mature dermal cells within the hair follicle.

Biernaskie and his team of researchers study dermal stem cells located within hair follicles. They are looking to better understand dermal stem cell function and find ways to use these cells to develop novel therapies for improved wound healing after injury, burns, disease or aging.

This study, co-authored by Raquel Gonzalez and Garrett Moffatt, shows that PDGF is key to maintaining a well-functioning stem cell population in skin. And in normal skin, if you dont have enough of it the stem cell pools start to shrink, meaning eventually the hair will no longer grow and wounds will not heal as well.

Its an important start in terms of how we might modulate these cells towards developing future therapies that could regenerate new dermal tissue or maintain hair growth says Biernaskie.

Biernaskies lab is looking at the potential role of stem cells in wound healing and the potential to stimulate these cells to improve skin regeneration, as opposed to forming scars.

The research is funded by a grant from Canadian Institutes for Health Research (CIHR) and the Calgary Firefighters Burn Treatment Society.

This article has been republished frommaterialsprovided bythe University of Calgary. Note: material may have been edited for length and content. For further information, please contact the cited source.

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'Signal' Crucial to Stem Cell Function in Hair Follicles Identified - Technology Networks

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Beauty elicits a deep, instinctive need to share from an early age. In fact, we defy you to find a more generous creature than a 7-year-old with a sparkly, new lip gloss in her backpack. Cooties be damned, she will prettify every second grader in sight. And we get it: weve built careers on swapping beauty secrets (and, okay, maybe a gloss or two).

We see this same communal spirit, shall we say, within the industry. Across brands and categories, this borrowing of ideas and technologies sparks trends and spawns knock-offs. In 2017, cosmetic ingredients flow freely, breaking all boundaries: Those once reserved for creams find their way into compacts . The same earthy clay and charcoal that purify pores can also whiten teeth and degrease roots.

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And were all for spreading the love when the science is legit. But the latest take-over hair-care companies co-opting buzzy skin-care actives, like peptides, stem cells, and antioxidants has us questioning just how translatable such technology truly is. Are we going too far in attempting to anti-age and revitalize something thats technicallydead?

Because, facts, after all: While skin and hair are composed of similar proteins and fats, living (innervated, blood-perfused) skin cells are in a constant state of renewal, rising up, plump and fresh, from the basal layer before eventually flattening out and sloughing off, says cosmetic chemist Randy Schueller . When injured or damaged, skin has the capacity to heal itself through normal biological processes, adds cosmetic chemist Jim Hammer . Hair, on the other hand, is dead at least the grown-out lengths of which we see and style and twirl. Hairs only vital part is nestled deep within the scalp: The cells of the hair follicles reproduce rapidly, pushing out hair fibers in the process, explains Melissa Piliang, a dermatologist at the Cleveland Clinic. But once sprouted from the scalp, those strands possess no living cells or repair mechanisms.

These distinctions have long dictated product goals: Skin care aims to affect biological processes, such as boosting cell turnover, increasing collagen synthesis, and inhibiting pigment production, says cosmetic chemist NiKita Wilson. Knowing this, we obsess over penetration can those actives actually get into the skin to do their good work? and chemists devise deep-diving delivery systems and penetration enhancers to guarantee performance. For hair, there really isnt much that can be done on a biological front short of improving the condition of the scalp to promote healthier strands, adds Wilson. It makes sense, then, that the majority of hair potions are designed to work on the surface, moisturizing and sealing hair to make it glassy, smooth, and full, while minimizing friction and breakage. While certain perfectly sized and shaped hydrators and proteins can seep past the hairs outer cuticle layer, into the deeper cortex, says Wilson, their effect is short-lived. Only chemicals like hair dyes and relaxers can alter hair in a lasting way.

So what of these new skin-inspired #hairgoals were hearing about, like anti-aging, anti-pollution, and high-tech hydration? Most of this is marketing driven with maybe a kernel of truth underneath, says Schueller. That kernel could be a single lab test showing a specific active, when dripped on cells in a glass dish, has some sort of effect which, by the way, doesnt mean it will work when delivered in final products on real people, he notes. Or perhaps a company finds a common water contaminant causes some degree of hair damage and then concocts an antioxidant to combat it. Even if the trauma to hair is miniscule compared to ordinary wear and tear, theyve now got enough data to make an antipollution claim and a new line of products to go with it, Schueller says. Across beauty lines, science sells: How do you make hair care more innovative? By using skin-care ingredients that elevate the level of sophistication, says cosmetic chemist Ginger King.

A successful tactic, judging from the proliferation of skin-inspired shampoos and serums on shelves, real and virtual. But why are we so eager to buy? Our population is aging, of course; yearning to maintain a healthy appearance, to look as young as we feel, says psychologist and marketing consultant Vivian Diller, PhD. Any product that promotes youth, well being, and vitality will be enormously appealing.

According to Rachel Anise, a communication studies professor at Golden West College in Huntington Beach, CA, there may also be social-psychology constructs at work here. People, on the whole, are largely swayed by what she calls the halo effect: We see stem cells, for example, as good at a basic level, and thereby extend their goodness to everything else in which they may be included, even if that reasoning is fundamentally flawed. And then theres the way we process advertising claims, she says, quickly and effortlessly, without thinking critically about them. Instead of questioningif or whyantioxidants may work on hair as they do skin, we'll just see a model with beautiful hair, acknowledge from past experience that antioxidants benefit skin, and automatically make the connection in two seconds, no less that they'll give our hair a youthful edge as well, says Anise.

Lucky for you, beauty analysis is sort of our jam. Here, we reality-check three adapted-for-hair-care claims:

THE CLAIM: Slowing down the aging process

WHAT IT MEANS FOR HAIR: The way hair ages has a lot to do with genetics and overall health, says dermatologist Lindsey Bordone. Hair tends to become finer over time as follicles miniaturize after menopause, she adds. It may turn coarse and brittle, and as pigment production wanes, fade to gray. On the scalp, cell turnover slows, giving rise to oil and flakes. UV rays a main cause of skin aging can degrade hairs proteins and color, but youd need a lot of concentrated sun exposure for that to be a real problem, says Schueller.

WHAT WORKS: Collagen and elastin proteins can cling to hairs surface, plumping and softening but only until your next shampoo. Plant-based stem cells essentially serve as antioxidants, curbing free radical damage, but their ability to thicken hair (or skin for that matter) is largely unproven. Surprisingly, peptides, which rev up collagen production, do show promise for aging hair. On the face, they plump skin to delay wrinkles and sagging. When applied to the scalp in a leave-on formula, they aid in anchoring the follicles to help strands remain firmly planted for a thicker head of hair, says Wilson. According to dermatologist Jeannette Graf , peptides are especially beneficial for thinning hair, which results from weakened scalp skin and circulation. Alongside peptides, she suggests looking for essential oils of lavender, orange, sage, and lemon peel to improve microcirculation, and enhance the delivery of nutrients to the hair bulb for healthier strands. As for sun care, hats trump UV filters. Think about how much sunscreen you need to put on skin to truly protect it, Schueller says. Its the same for hair and scalp: Youd need a tremendous amount, and whos going to apply that heavy of a coating?

THE CLAIM: Combatting pollution

WHAT IT MEANS FOR HAIR: Every day, our hair, like our skin, is exposed to free radical-inciting pollutants in the air and water. According to dermatologist Michelle Henry, all types of pollution, including particulate matter, dust, smoke, nickel, lead, and sulfur dioxide and nitrogen dioxide [emitted from vehicles and power plants] can settle on the scalp and hair causing significant inflammation, dryness, dullness, even hair loss.If that werent devastating enough, ground-level smog, which contains high levels of ozone, can bleach our hair color, says Hammer. Other contaminants may rob it completely: Premature graying is seen more in smokers than non-smokers as a result of oxidative stress, says dermatologist Nicole Rogers, adding that free radicals from all sources not just cigarettes can affect the follicles' ability to repigment. That said, pollutions precise toll on hair is unknown. I havent seen a ton of research proving its a major threat, says Schueller. Of all the things that can harm hair chemicals, brushing, heat Id imagine free radicals are low on the list.

WHAT WORKS: With thinning and graying as potential consequences, why take chances? While only a diet rich in free radical-quelching antioxidants can truly defend hair at a follicular level, certain products and practices can help safeguard strands from the environment. For starters, washing your hair thoroughly, and with sufficient frequency for your hair type, is key to curbing the scalp inflammation that contributes to hair loss, says Henry.Shampoos with chelating agents, like EDTA, will gently extract heavy metals (found in car exhaust, cigarette smoke, hard water). Youll also want to look for leave-ins with concentrated doses of antioxidants (think: vitamins, tea extracts, idebenone, resveratrol) to neutralize free radicals, and strand-coating silicones, proteins, and polymers, which provide a physical barrier, walling off hair from pollutants, says Hammer.

THE CLAIM: Healing hydration

WHAT IT MEANS FOR HAIR: With a rich blood supply and an abundance of oil glands, the scalp is an extension of our skin, says dermatologist Francesca Fusco . It shares the same lipids and humectants, and is equally prone to dryness and irritation. Hair suffers from dehydration, too, particularly when its cuticle is eroded (by water, heat, and chemicals).

WHAT WORKS: Hyaluronic acid, a water-binding humectant, and ceramides, moisture-retaining lipids, are both found naturally in the skin (and in countless creams and serums). Since they improve the functioning of skin cells, making them more resilient and efficient, both can help keep the scalp in peak condition. When applied to hair (again, leave-on products work best), they coat strands to lock in moisture while also shielding from heat and styling damage, says Rogers, noting a 2002 study in which ceramides were shown to bind to African hair, helping to reduce breakage. Coconut oil and panthenol (a B vitamin) also nourish the scalp, and unlike most other ingredients, can penetrate inside the hair shaft, hydrating from within to enhance pliability, and keeping the cuticle tight and intact.

Bottom Line: The secret to beautiful hair is a healthy scalp. When the scalp is out of whack meaning theres poor circulation, an oil imbalance, or a build-up of cells we see not only flakes and inflammation, but hair that looks and feels unhealthy, and may even shed before its time, says Fusco. Seek out proven actives that take aim at the scalp (many of which do hail from the skin realm): dandruff-fighting pyrithione zinc (in Doves new DermaCare Scalp collection); clays that absorb excess oil and calm irritation (like those in LOral Paris Extraordinary Clay Pre-Shampoo Mask ); exfoliating salicylic acid or willowbark extract, which keep cells shedding at a normal clip to prevent pile-ups; and the aforementioned hydrators to soothe and replenish dry, depleted follicles.

Check out the best new drugstore beauty products of 2017:

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Trendy Skin Care Ingredients Are Being Added to Hair Care Products - Allure Magazine

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Quartz

Scientists are using gene editing to create the perfect tomato for your salad Quartz In a study published in the journal Cell on May 18, geneticist Zachary Lippman of Cold Spring Harbor Laboratory explains his research team's efforts to fix mutated tomatoes using CRISPR gene editing technology. By identifying the genes associated with ...

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Scientists are using gene editing to create the perfect tomato for your salad - Quartz

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Denver, Colo., May 23, 2017 / 03:04 am (CNA/EWTN News).- With plans for the first human head transplant surgery looming in the next year, a lead doctor on the formidable project has high hopes for the procedure. Along with the aim of finding a new body for a yet-to-be-selected patient, the physician says that the surgery as a first step toward immortality will effectively disprove religion. But Catholic critics have called into question not only the ethics of such a risky procedure, but the dubious claim that such a development would render belief in God irrelevant.

The actual trying of the surgery at this point I think would be unethical because of the tremendous risk involved, and it is an unproven surgery, Dr. Paul Scherz, assistant professor of moral theology and ethics at The Catholic University of America, told CNA.

Sherz made his remarks following the news that Italian doctor Sergio Canavero is aiming to carry out the first human head transplant surgery within the next 10 months. It's a process Canavero hopes will pave the way for the process of transplanting cryogenically frozen brains and ultimately, in his view, to the eradication of death.

Canavero serves as director of Turin Advanced Neuromodulation Group and has teamed up with Harbin Medical Centre and Doctor Xiaoping Ren, an orthopedic surgeon who was involved with the first successful hand transplant in the U.S. The first surgical attempt for the head transplant is expected to take place in China, where the group says they're more likely to find a donor body.

Cryonics involves the freezing of the brain or even the whole body of patients, with expectations that future science will have the means to restore the frozen tissue and extend life. Because conscious minds will have experienced life outside of death, Canavero said the surgery would then remove the fear of death and the people's need for religion. He said if the process succeeds, religions will be swept away forever.

However, Sherz responded that even if the surgery was a success, it would not disprove the Catholic faith. There is nothing in the Catholic tradition of how we understand the soul that would think that if you moved a head or moved the brain that that wouldnt allow the person to come back to life, he said.

Turin Advanced Neuromodulation Group has already claimed that a successful head transplant has been carried out on a monkey, but not all scientists agree that the operation can be recorded as a success. Before the monkey's head was stitched back together, it was removed, cooled, and the blood of the transplant body was cross circulated with an outside source. Canavero and his group claimed the supply of blood was then connected to prove the surgery succeeded without brain damage, but the spinal cord was left unattached.

How the connected blood supply proves the surgery is possible without brain damage was not described, and many bioethicists are skeptical of the publication of the surgery's success without proper peer review and of the issues around the severed spine. Because the technology has not yet been developed, the bioethicists worry that the severed spine may never be reconstructed, leaving the patient worse off than before.

Despite the pervasive belief in the surgery's failure, Canavero claims there's a 90 percent chance that the human head transplant will succeed. And not only that, its success would allow humans to no longer need to be afraid of death.

Father Tad Pacholczyk, who serves as a bioethicist for the National Catholic Bioethics Center, disagreed with Canavero's definition of being brought back to life. He said to assume death as a necessary product of either the head surgery or brain surgery is gullible and mistaken, as there is potential for the patient to be merely unconscious.

The patient undergoing the head transplant is not dead, only unconscious, he told CNA. There is not any 'bringing back to life'There is merely a restoration of consciousness, briefly lost during the movement of the head from one human body to the other.

Scherz also said that the Church accepts an intimate and mysterious relationship between soul and body, and that the procedure's success wouldn't necessary disprove the soul or religion. Our neurological tissue has important part to play in our soulThe soul is always intimately related to the body. We are not just souls that are disembodied, right? We are embodied spirits or spirited bodies.

Most physicians agree that the proposed surgery's success rate is infinitesimal, and they've questioned the morality of a procedure that's doomed to fail and the unrealistic hope life extension projects could give to people. I am concerned that the rights of vulnerable patients undergoing cryonics cannot be protected indefinitely, Dr. Channa Jayasena, a lecturer in Reproductive Endocrinology at Imperial College in London, told the Telegraph. Cryonics, she said, has risks for the patient, poses ethical issues for society, is highly expensive, but has no proven benefit.

And the hope for immortal life, Scherz weighed in, isn't a realistic desire in a fallen world. Living forever in bodily form is not going to satisfy anyone, he said. If the goal is not to help someone to get back bodily movement or things like that, but to try to live forever on this earth, then I think if you really want to get over the fear of death then you will have to come to terms with the fact that we are mortal. That what's going to help you to live a better life because you are going to be willing to give your life to things like service.

In fact, he said that people in transhumanist movements have admitted they would most likely avoid risky behavior in order to preserve their lives. If life extension projects come into being there is so much more to lose and you committed yourself to trying to live on this earth for as long as possible, which stands in contrast to the Catholic tradition and a lot of the philosophical traditions, Scherz noted.

Continue reading here:
Why head transplants won't disprove the existence of God | Angelus - The Tidings

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Newswise LOS ANGELES Jay R. Lieberman, MD, chair and professor of orthopedic surgery at the Keck School of Medicine of the University of Southern California has received a five-year, $2.2 million grant from the National Institutes of Healths National Institute of Arthritis and Musculoskeletal and Skin Diseases to research gene therapy to enhance repair of extensive bone injuries. Examples of these types of injuries include fractures with extensive bone loss, non-healing fractures, failed spinal fusion and revision of total joint replacement.

Lieberman will genetically manipulate human bone marrow cells to overproduce bone morphogenetic protein (BMP), which is a protein that spurs progenitor cells to produce bone.

There are a number of bone injuries that are very difficult to repair and lack satisfactory solutions, Lieberman says. My goal with this grant is to determine whether genetically modifying human bone marrow cells to overproduce BMP will help heal large bone defects in an animal model and, ultimately, provide a better alternative for repairs in humans.

Liebermans study will determine the efficacy and safety of the gene therapy as well as establish a cellular dose of the genetically manipulated cells that can be scaled up for potential use in humans.

An abstract of the grant, 2R01AR057076-06A1, is available on the NIH RePORTER website.

###

ABOUT THE KECK SCHOOL OF MEDICINE OF USC

Founded in 1885, the Keck School of Medicine of USC is among the nations leaders in innovative patient care, scientific discovery, education, and community service. It is part of Keck Medicine of USC, the University of Southern California's medical enterprise, one of only two university-owned academic medical centers in the Los Angeles area. This includes the Keck Medical Center of USC, composed of the Keck Hospital of USC and the USC Norris Cancer Hospital. The two world-class, USC-owned hospitals are staffed by more than 500 physicians who are faculty at the Keck School. The school today has approximately 1,650 full-time faculty members and voluntary faculty of more than 2,400 physicians. These faculty direct the education of approximately 700 medical students and 1,000 students pursuing graduate and post-graduate degrees. The school trains more than 900 resident physicians in more than 50 specialty or subspecialty programs and is the largest educator of physicians practicing in Southern California. Together, the school's faculty and residents serve more than 1.5 million patients each year at Keck Hospital of USC and USC Norris Cancer Hospital, as well as USC-affiliated hospitals Childrens Hospital Los Angeles and Los Angeles County + USC Medical Center. Keck School faculty also conduct research and teach at several research centers and institutes, including the USC Norris Comprehensive Cancer Center, the Zilkha Neurogenetic Institute, the Eli and Edythe Broad Center for Stem Cell Research and Regenerative Medicine at USC, the USC Cardiovascular Thoracic Institute, the USC Roski Eye Institute and the USC Institute of Urology.

In 2017, U.S. News & World Report ranked Keck School of Medicine among the Top 40 medical schools in the country. For more information, go to keck.usc.edu.

###

This press release references support by the National Institutes of Health under award number 2R01AR057076-06A1 ($2,284,028 over five years). One hundred percent of the projects funding will be federally funded.

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Keck School of Medicine of USC Receives $2.2 Million NIH Grant to Fund Research on Healing Difficult Bone Injuries - Newswise (press release)

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March 2012

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Additional Resources American Urological Association Foundation

What is the role of testosterone in mens health?

Testosterone is the most important sex hormone that men have. It is responsible for the typical male characteristics, such as facial, pubic, and body hair as well as muscle. This hormone also helps maintain sex drive, sperm production, and bone health. The brain and pituitary gland (a small gland at the base of the brain) control the production of testosterone by the testes.

In the short term, low testosterone (also called hypogonadism) can cause

Over time, low testosterone may cause a man to lose body hair, muscle bulk, and strength and to gain body fat. Chronic (long-term) low testosterone may also cause weak bones (osteoporosis), mood changes, less energy, and smaller testes. Signs and symptoms (what you see and feel) vary from person to person.

What causes low testosterone?

Low testosterone can result from

Low testosterone is common in older men. In many cases, the cause is not known.

How is low testosterone diagnosed?

During a physical exam, your doctor will examine your body hair, size of your breasts and penis, and the size and consistency of the testes and scrotum. Your doctor may check for loss of side vision, which could indicate a pituitary tumor, a rare cause of low testosterone.

Your doctor will also use blood tests to see if your total testosterone level is low. The normal range is generally 300 to 1,000 ng/dL, but this depends on the lab that conducts the test. To get a diagnosis of low testosterone, you may need more than one early morning (710 AM) blood test and, sometimes, tests of pituitary gland hormones.

If you have symptoms of low testosterone, your doctor may suggest that you talk with an endocrinologist. This expert in hormones can help find the cause. Be open with your doctor about your medical history, all prescription and nonprescription drugs you are now taking, sexual problems, and any major changes in your life.

How is low testosterone treated?

Testosterone replacement therapy can improve sexual interest, erections, mood and energy, body hair growth, bone density, and muscle mass. There are several ways to replace testosterone:

The best method will depend on your preference and tolerance, and the cost.

There are risks with long-term use of testosterone. The most serious possible risk is prostate cancer. African American men, men over 40 years of age who have close relatives with prostate cancer, and all men over 50 years of age need monitoring for prostate cancer during testosterone treatment. Men with known or suspected prostate cancer, or with breast cancer, should not receive testosterone treatment.

Other possible risks of testosterone treatment include

Questions to ask your doctor

More here:
Hypogonadism Hormone Health Network

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The Harvard Stem Cell Institute is developing new techniques to grow and transplant heart cells, replacing those lost to cardiovascular disease.

The greatest threat to the long-term health and well-being of people living with diabetes is cardiovascular disease. The diabetic population as a whole is two to four times more likely than non-diabetics to develop heart disease or suffer a stroke. Type 1 diabetes, which is most often diagnosed in childhood and adolescence, is particularly devastating, as one New England Journal of Medicine study associated it with a ten-fold increase in cardiovascular disease.

The human adult heart has about five billion heart cells, all pulsing as a coordinated orchestra with every heartbeat. These cells can be killed by high blood pressure, blood clots, heart attacks, and other byproducts of cardiovascular disease. The heart has an age-related block in its ability to make new heart cells, so that damaged cells are not replaced in the latter half of life, precisely when we need them the most. A typical patient with heart failure has lost over a billion heart cells.

Harvard Stem Cell Institute (HSCI) investigators are developing ways to make replacement heart cells and provide them with the right cues so that the new cells play as needed in the orchestra.

Both embryonic stem cells and induced pluripotent stem cells mature cells that are manipulated back to a stem cell state can be harnessed to create new heart cells. The difficulty is that the heart cells made with stem cells resemble the heart cells of an infant, rather than adult heart cells. To function in adult hearts, the new heart cells must mature and then be able to survive within the constantly beating environment of the heart.

The scientific community has generated the technology to make heart cells that are immature, but very few heart cells derived from stem cells integrate into the normal heart tissue as mature heart cells. At the HSCI, our researchers are focused on understanding how to take these new heart cells all the way to maturity and stability, so they can be used as an effective therapy.

HSCI scientists are also developing ways of using the bodys heart matrix the rich, intricate scaffold of the heart that serves as the permanent home for our heart cells to guide maturation and prolong the survival of heart cells derived from stem cells after implantation.

The heart matrix is like the sheet music for the heart orchestra. It tells the heart cells where to sit and how to function with their neighbors so that a heartbeat is in sync. The problem of redrawing these matrix-directed instructions from scratch once seemed too daunting to tackle.

By breaking down the hearts scaffold material into thousands of individual chemicals, HSCI researchers hope to rebuild the environments that allow immature heart cells to mature. Armed with this knowledge, it will be possible to construct real adult heart tissue in the laboratory, as well as realistic approaches to transplanting patient-specific heart cells into their damaged organs.

In addition to these ambitious projects, HSCI is pursuing interim objectives before reaching the ultimate goal of reconstructing the heart. For example, a recent study led to the identification of a blood circulating factor that declines with age but, when injected, can reverse age-related heart enlargement and accompanying heart failure. If this is successful in human studies, we will have identified a new therapeutic approach for the aging heart.

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Heart Disease | Harvard Stem Cell Institute (HSCI)

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Todd J. Herron, BS, PhD Director of the Frankel Cardiovascular Center's Cardiovascular Regeneration Core Laboratory and Assistant Research Professor at the University of Michigan Center for Arrhythmia

Yorba Linda, Ca (PRWEB) May 23, 2017

Pluripotent stem cells (PSCs) offer an unlimited source of human cardiovascular cells for research and the development of cardiac regeneration therapies. The development of highly efficient cardiac-directed differentiation methods makes it possible to generate large numbers of cardiomyocytes (hPSC-CMs). Due to varying differentiation efficiencies, further enrichment of CM populations for downstream applications is essential.

Recently, a CM-specific cell surface marker called SIRPa (signal-regulatory protein alpha, also termed CD172a) was reported to be a useful tool for flow sorting of human stem cellderived CMs. However, our expression analysis revealed that SIRPa only labels a subpopulation of CMs indicated by cardiac Troponin T (cTnT) expression. Moreover, SIRPa is also expressed on a sub population of non-CMs, hence making SIRa an inadequate marker to enrich PSC-derived CMs.

In this webinar, sponsored by the team at Miltenyi Biotec, participants will have a chance to review human induced pluripotent stem cell derivation, cardiac directed differentiation to human pluripotent stem cell cardiomyocytes (hPSC-CMs), enrichment of hPSC-CMs and subsequent formation of 2D monolayers of electrically connected cells. They will also learn of the generation of purified human induced pluripotent stem cell derived cardiomyocyte.

The speaker for this event will be Dr. Todd J. Herron, director of the Frankel Cardiovascular Center's Cardiovascular Regeneration Core Laboratory and Assistant Research Professor at the University of Michigan Center for Arrhythmia Research.

Herron currently serves as the director of the Frankel Cardiovascular Center's Cardiovascular Regeneration Core Laboratory, as well as holding a position on the faculty in the University of Michigan Medical School and has appointments in the Department of Internal Medicine and Molecular & Integrative Physiology as Associate Research Scientist. His research is focused on the complex interplay between cardiac electrical excitation and contractile force generation-a process known classically as excitation-contraction coupling.

LabRoots will host the event June 7, 2017, beginning at 9 a.m. PDT, 12 p.m. EDT. To read more about this event, learn about the continuing education credits offered, or to register for free, click here.

ABOUT MILTENYI BIOTEC Miltenyi Biotec is a global provider of products and services that advance biomedical research and cellular therapy. The companys innovative tools support research at every level, from basic research to translational research to clinical application. This integrated portfolio enables scientists and clinicians to obtain, analyze, and utilize the cell. Miltenyi Biotecs technologies cover techniques of sample preparation, cell isolation, cell sorting, flow cytometry, cell culture, molecular analysis, and preclinical imaging. Their more than 25 years of expertise spans research areas including immunology, stem cell biology, neuroscience, and cancer, and clinical research areas like hematology, graft engineering, and apheresis. In their commitment to the scientific community, Miltenyi Biotec also offers comprehensive scientific support, consultation, and expert training. Today, Miltenyi Biotec has more than 1,500 employees in 25 countries all dedicated to helping researchers and clinicians around the world make a greater impact on science and health.

ABOUT LABROOTS LabRoots is the leading scientific social networking website, which provides daily scientific trending news and science-themed apparel, as well as produces educational virtual events and webinars, on the latest discoveries and advancements in science. Contributing to the advancement of science through content sharing capabilities, LabRoots is a powerful advocate in amplifying global networks and communities. Founded in 2008, LabRoots emphasizes digital innovation in scientific collaboration and learning, and is a primary source for current scientific news, webinars, virtual conferences, and more. LabRoots has grown into the worlds largest series of virtual events within the Life Sciences and Clinical Diagnostics community.

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Miltenyi Biotec Showcases the Generation of Purified Human iPSC Derived Cardiomyocytes - PR Web (press release)

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On a cold, bright January morning I walked south across Westminster Bridge to St Thomas Hospital, an institution with a proud tradition of innovation: I was there to observe a procedure generally regarded as the greatest advance in cardiac surgery since the turn of the millennium and one that can be performed without a surgeon.

The patient was a man in his 80s with aortic stenosis, a narrowed valve which was restricting outflow from the left ventricle into the aorta. His heart struggled to pump sufficient blood through the reduced aperture, and the muscle of the affected ventricle had thickened as the organ tried to compensate. If left unchecked, this would eventually lead to heart failure. For a healthier patient the solution would be simple: an operation to remove the diseased valve and replace it with a prosthesis. But the mans age and a long list of other medical conditions made open-heart surgery out of the question. Happily, for the last few years, another option has been available for such high-risk patients: transcatheter aortic valve implantation, known as TAVI for short.

This is a non-invasive procedure, and takes place not in an operating theatre but in the catheterisation laboratory, known as the cath lab. When I got there, wearing a heavy lead gown to protect me from X-rays, the patient was already lying on the table. He would remain awake throughout the procedure, receiving only a sedative and a powerful analgesic. I was shown the valve to be implanted, three leaflets fashioned from bovine pericardium (a tough membrane from around the heart of a cow), fixed inside a collapsible metal stent. After being soaked in saline it was crimped on to a balloon catheter and squeezed, from the size and shape of a lipstick, into a long, thin object like a pencil.

The consultant cardiologist, Bernard Prendergast, had already threaded a guidewire through an incision in the patients groin, entering the femoral artery and then the aorta, until the tip of the wire had arrived at the diseased aortic valve. The catheter, with its precious cargo, was then placed over the guidewire and pushed gently up the aorta. When it reached the upper part of the vessel we could track its progress on one of the large X-ray screens above the table. We watched intently as the metal stent described a slow curve around the aortic arch before coming to rest just above the heart.

There was a pause as the team checked everything was ready, while on the screen the silhouette of the furled valve oscillated gently as it was buffeted by pulses of high-pressure arterial blood. When Prendergast was satisfied that the catheter was precisely aligned with the aortic valve, he pressed a button to inflate the tiny balloon. As it expanded it forced the metal stent outwards and back to its normal diameter, and on the X-ray monitor it suddenly snapped into position, firmly anchored at the top of the ventricle. For a second or two the patient became agitated as the balloon obstructed the aorta and stopped the flow of blood to his brain; but as soon as it was deflated he became calm again.

Prendergast and his colleagues peered at the monitors to check the positioning of the device. In a conventional operation the diseased valve would be excised before the prosthesis was sewn in; during a TAVI procedure the old valve is left untouched and the new one simply placed inside it. This makes correct placement vital, since unless the device fits snugly there may be a leak around its edge. The X-ray picture showed that the new valve was securely anchored and moving in unison with the heart. Satisfied that everything had gone according to plan, Prendergast removed the catheter and announced the good news in a voice that was probably audible on the other side of the river. Just minutes after being given a new heart valve, the patient raised an arm from under the drapes and shook the cardiologists hand warmly. The entire procedure had taken less than an hour.

According to many experts, this is what the future will look like. Though available for little more than a decade, TAVI is already having a dramatic impact on surgical practice: in Germany the majority of aortic valve replacements, more than 10,000 a year, are now performed using the catheter rather than the scalpel.

In the UK, the figure is much lower, since the procedure is still significantly more expensive than surgery this is largely down to the cost of the valve itself, which can be as much as 20,000 for a single device. But as the manufacturers recoup their initial outlay on research and development, it is likely to become more affordable and its advantages are numerous. Early results suggest that it is every bit as effective as open-heart surgery, without many of surgerys undesirable aspects: the large chest incision, the heart-lung machine, the long period of post-operative recovery.

The essential idea of TAVI was first suggested more than half a century ago. In 1965, Hywel Davies, a cardiologist at Guys Hospital in London, was mulling over the problem of aortic regurgitation, in which blood flows backwards from the aorta into the heart. He was looking for a short-term therapy for patients too sick for immediate surgery something that would allow them to recover for a few days or weeks, until they were strong enough to undergo an operation. He hit upon the idea of a temporary device that could be inserted through a blood vessel, and designed a simple artificial valve resembling a conical parachute. Because it was made from fabric, it could be collapsed and mounted on to a catheter. It was inserted with the top of the parachute uppermost, so that any backwards flow would be caught by its inside surface like air hitting the underside of a real parachute canopy. As the fabric filled with blood it would balloon outwards, sealing the vessel and stopping most of the anomalous blood flow.

This was a truly imaginative suggestion, made at a time when catheter therapies had barely been conceived of, let alone tested. But, in tests on dogs, Davies found that his prototype tended to provoke blood clots and he was never able to use it on a patient.

Another two decades passed before anybody considered anything similar. That moment came in 1988, when a trainee cardiologist from Denmark, Henning Rud Andersen, was at a conference in Arizona, attending a lecture about coronary artery stenting. It was the first he had heard of the technique, which at the time had been used in only a few dozen patients, and as he sat in the auditorium he had a thought, which at first he dismissed as ridiculous: why not make a bigger stent, put a valve in the middle of it, and implant it into the heart via a catheter? On reflection, he realised that this was not such an absurd idea, and when he returned home to Denmark he visited a local butcher to buy a supply of pig hearts. Working in a pokey room in the basement of his hospital with basic tools obtained from a local DIY warehouse, Andersen constructed his first experimental prototypes. He began by cutting out the aortic valves from the pig hearts, mounted each inside a home-made metal lattice then compressed the whole contraption around a balloon.

Within a few months Andersen was ready to test the device in animals, and on 1 May 1989 he implanted the first in a pig. It thrived with its prosthesis, and Andersen assumed that his colleagues would be excited by his works obvious clinical potential. But nobody was prepared to take the concept seriously folding up a valve and then unfurling it inside the heart seemed wilfully eccentric and it took him several years to find a journal willing to publish his research.

When his paper was finally published in 1992, none of the major biotechnology firms showed any interest in developing the device. Andersens crazy idea worked, but still it sank without trace.

Andersen sold his patent and moved on to other things. But at the turn of the century there was a sudden explosion of interest in the idea of valve implantation via catheter. In 2000, a heart specialist in London, Philipp Bonhoeffer, replaced the diseased pulmonary valve of a 12-year-old boy, using a valve taken from a cows jugular vein, which had been mounted in a stent and put in position using a balloon catheter.

In France, another cardiologist was already working on doing the same for the aortic valve. Alain Cribier had been developing novel catheter therapies for years; it was his company that bought Andersens patent in 1995, and Cribier had persisted with the idea even after one potential investor told him that TAVI was the most stupid project ever heard of.

Eventually, Cribier managed to raise the necessary funds for development and long-term testing, and by 2000 had a working prototype. Rather than use an entire valve cut from a dead heart, as Andersen had, Cribier built one from bovine pericardium, mounted in a collapsible stainless-steel stent. Prototypes were implanted in sheep to test their durability: after two-and-a-half years, during which they opened and closed more than 100m times, the valves still worked perfectly.

Cribier was ready to test the device in humans, but his first patient could not be eligible for conventional surgical valve replacement, which is safe and highly effective: to test an unproven new procedure on such a patient would be to expose them to unnecessary risk.

In early 2002, he was introduced to a 57-year-old man who was, in surgical terms, a hopeless case. He had catastrophic aortic stenosis which had so weakened his heart that with each stroke it could pump less than a quarter of the normal volume of blood; in addition, the blood vessels of his extremities were ravaged by atherosclerosis, and he had chronic pancreatitis and lung cancer. Several surgeons had declined to operate on him, and his referral to Cribiers clinic in Rouen was a final roll of the dice. An initial attempt to open the stenotic valve using a simple balloon catheter failed, and a week after this treatment Cribier recorded in his notes that his patient was near death, with his heart barely functioning. The mans family agreed that an experimental treatment was preferable to none at all, and on 16 April he became the first person to receive a new aortic valve without open-heart surgery.

Over the next couple of days the patients condition improved dramatically: he was able to get out of bed, and the signs of heart failure began to retreat. But shortly afterwards complications arose, most seriously a deterioration in the condition of the blood vessels in his right leg, which had to be amputated 10 weeks later. Infection set in, and four months after the operation, he died.

He had not lived long nobody expected him to but the episode had proved the feasibility of the approach, with clear short-term benefit to the patient. When Cribier presented a video of the operation to colleagues they sat in stupefied silence, realising that they were watching something that would change the nature of heart surgery.

When surgeons and cardiologists overcame their initial scepticism about TAVI they quickly realised that it opened up a vista of exciting new surgical possibilities. As well as replacing diseased valves it is now also possible to repair them, using clever imitations of the techniques used by surgeons. The technology is still in its infancy, but many experts believe that this will eventually become the default option for valvular disease, making surgery increasingly rare.

While TAVI is impressive, there is one even more spectacular example of the capabilities of the catheter. Paediatric cardiologists at a few specialist centres have recently started using it to break the last taboo of heart surgery operating on an unborn child. Nowhere is the progress of cardiac surgery more stunning than in the field of congenital heart disease. Malformations of the heart are the most common form of birth defect, with as many as 5% of all babies born with some sort of cardiac anomaly though most of these will cause no serious, lasting problems. The heart is especially prone to abnormal development in the womb, with a myriad of possible ways in which its structures can be distorted or transposed. Over several decades, specialists have managed to find ways of taming most; but one that remains a significant challenge to even the best surgeon is hypoplastic left heart syndrome (HLHS), in which the entire left side of the heart fails to develop properly. The ventricle and aorta are much smaller than they should be, and the mitral valve is either absent or undersized. Until the early 1980s this was a defect that killed babies within days of birth, but a sequence of complex palliative operations now makes it possible for many to live into adulthood.

Because their left ventricle is incapable of propelling oxygenated blood into the body, babies born with HLHS can only survive if there is some communication between the pulmonary and systemic circulations, allowing the right ventricle to pump blood both to the lungs and to the rest of the body. Some children with HLHS also have an atrial septal defect (ASD), a persistent hole in the tissue between the atria of the heart which improves their chances of survival by increasing the amount of oxygenated blood that reaches the sole functioning pumping chamber. When surgeons realised that this defect conferred a survival benefit in babies with HLHS, they began to create one artificially in those with an intact septum, usually a few hours after birth. But it was already too late: elevated blood pressure was causing permanent damage to the delicate vessels of the lungs while these babies still in the womb.

The logical albeit risky response was to intervene even earlier. In 2000, a team at Boston Childrens Hospital adopted a new procedure to create an ASD during the final trimester of pregnancy: they would deliberately create one heart defect in order to treat another. A needle was passed through the wall of the uterus and into the babys heart, and a balloon catheter used to create a hole between the left and right atria. This reduced the pressures in the pulmonary circulation and hence limited the damage to the lungs; but the tissues of a growing foetus have a remarkable ability to repair themselves, and the artificially created hole would often heal within a few weeks. Cardiologists needed to find a way of keeping it open until birth, when surgeons would be able to perform a more comprehensive repair.

In September 2005 a couple from Virginia, Angela and Jay VanDerwerken, visited their local hospital for a routine antenatal scan. They were devastated to learn that their unborn child had HLHS, and the prognosis was poor. The ultrasound pictures revealed an intact septum, making it likely that even before birth her lungs would be damaged beyond repair. They were told that they could either terminate the pregnancy or accept that their daughter would have to undergo open-heart surgery within hours of her birth, with only a 20% chance that she would survive.

Devastated, the VanDerwerkens returned home, where Angela researched the condition online. Although few hospitals offered any treatment for HLHS, she found several references to the Boston foetal cardiac intervention programme, the team of doctors that had pioneered the use of the balloon catheter during pregnancy.

They arranged an appointment with Wayne Tworetzky, the director of foetal cardiology at Boston Childrens Hospital, who performed a scan and confirmed that their unborn childs condition was treatable. A greying, softly spoken South African, Tworetzky explained that his team had recently developed a new procedure, but that it had never been tested on a patient. It would mean not just making a hole in the septum, but also inserting a device to prevent it from closing. The VanDerwerkens had few qualms about accepting the opportunity: the alternatives gave their daughter a negligible chance of life.

The procedure took place at Brigham and Womens Hospital in Boston on 7 November 2005, 30 weeks into the pregnancy, in a crowded operating theatre. Sixteen doctors, with a range of specialisms, took part: cardiologists, surgeons, and four anaesthetists two to look after the mother, two for her unborn child. Mother and child needed to be completely immobilised during a delicate procedure lasting several hours, so both were given a general anaesthetic. The team watched on the screen of an ultrasound scanner as a thin needle was guided through the wall of the uterus, then the foetuss chest and finally into her heart an object the size of a grape.

A guidewire was placed in the cardiac chambers, then a tiny balloon catheter was inserted and used to create an opening in the atrial septum. This had all been done before; but now the cardiologists added a refinement. The balloon was withdrawn, then returned to the heart, this time loaded with a 2.5 millimetre stent that was set in the opening between the left and right atria. There was a charged silence as the balloon was inflated to expand the stent; then, as the team saw on the monitor that blood was flowing freely through the aperture, the room erupted in cheers.

Grace VanDerwerken was born in early January after a normal labour, and shortly afterwards underwent open-heart surgery. After a fortnight she was allowed home, her healthy pink complexion proving that the interventions had succeeded in producing a functional circulation.

But just when she seemed to be out of danger, Grace died suddenly at the age of 36 days not as a consequence of the surgery, but from a rare arrhythmia, a complication of HLHS that occurs in just 5%. This was the cruellest luck, when she had seemingly overcome the grim odds against her. Her death was a tragic loss, but her parents courage had brought about a new era in foetal surgery.

Much of the most exciting contemporary research focuses on the greatest, most fundamental cardiac question of all: what can the surgeon do about the failing heart? Half a century after Christiaan Barnard performed the first human heart transplant, transplantation remains the gold standard of care for patients in irreversible heart failure once drugs have ceased to be effective. It is an excellent operation, too, with patients surviving an average of 15 years. But it will never be the panacea that many predicted, because there just arent enough donor hearts to go round.

With too few organs available, surgeons have had to think laterally. As a result, a new generation of artificial hearts is now in development. Several companies are now working on artificial hearts with tiny rotary electrical motors. In addition to being much smaller and more efficient than pneumatic pumps, these devices are far more durable, since the rotors that impel the blood are suspended magnetically and are not subject to the wear and tear caused by friction. Animal trials have shown promising results, but, as yet, none of these have been implanted in a patient.

Another type of total artificial heart, as such devices are known, has, however, recently been tested in humans. Alain Carpentier, an eminent French surgeon still active in his ninth decade, has collaborated with engineers from the French aeronautical firm Airbus to design a pulsatile, hydraulically powered device whose unique feature is the use of bioprosthetic materials both organic and synthetic matter. Unlike earlier artificial hearts, its design mimics the shape of the natural organ; the internal surfaces are lined with preserved bovine pericardial tissue, a biological surface far kinder to the red blood cells than the polymers previously used. Carpentiers artificial heart was first implanted in December 2013. Although the first four patients have since died two following component failures the results were encouraging, and a larger clinical trial is now under way.

One drawback to the artificial heart still leads many surgeons to dismiss the entire concept out of hand: the price tag. These high-precision devices cost in excess of 100,000 each, and no healthcare service in the world, publicly or privately funded, could afford to provide them to everybody in need of one. And there is one still more tantalising notion: that we will one day be able to engineer spare parts for the heart, or even an entire organ, in the laboratory.

In the 1980s, surgeons began to fabricate artificial skin for burns patients, seeding sheets of collagen or polymer with specialised cells in the hope that they would multiply and form a skin-like protective layer. But researchers had loftier ambitions, and a new field tissue engineering began to emerge.

High on the list of priorities for tissue engineers was the creation of artificial blood vessels, which would have applications across the full range of surgical specialisms. In 1999 surgeons in Tokyo performed a remarkable operation in which they gave a four-year-old girl a new artery grown from cells taken from elsewhere in her body. She had been born with a rare congenital defect which had completely obliterated the right branch of her pulmonary artery, the vessel conveying blood to the right lung. A short section of vein was excised from her leg, and cells from its inside wall were removed in the laboratory. They were then left to multiply in a bioreactor, a vessel that bathed them in a warm nutrient broth, simulating conditions inside the body.

After eight weeks, they had increased in number to more than 12m, and were used to seed the inside of a polymer tube which functioned as a scaffold for the new vessel. The tissue was allowed to continue growing for 10 days, and then the graft was transplanted. Two months later the polymer scaffold around the tissue, designed to break down inside the body, had completely dissolved, leaving only new tissue that would it was hoped grow with the patient.

At the turn of the millennium, a new world of possibility opened up when researchers gained a powerful new tool: stem cell technology. Stem cells are not specialised to one function but have the potential to develop into many different tissue types. One type of stem cell is found in growing embryos, and another in parts of the adult body, including the bone marrow (where they generate the cells of the blood and immune system) and skin. In 1998 James Thomson, a biologist at the University of Wisconsin, succeeded in isolating stem cells from human embryos and growing them in the laboratory.

But an arguably even more important breakthrough came nine years later, when Shinya Yamanaka, a researcher at Kyoto University, showed that it was possible to genetically reprogram skin cells and convert them into stem cells. The implications were enormous. In theory, it would now be possible to harvest mature, specialised cells from a patient, reprogram them as stem cells, then choose which type of tissue they would become.

Sanjay Sinha, a cardiologist at the University of Cambridge, is attempting to grow a patch of artificial myocardium (heart muscle tissue) in the laboratory for later implantation in the operating theatre. His technique starts with undifferentiated stem cells, which are then encouraged to develop into several types of specialised cell. These are then seeded on to a scaffold made from collagen, a tough protein found in connective tissue. The presence of several different cell types means that when they have had time to proliferate, the new tissue will develop its own blood supply.

Clinical trials are still some years away, but Sinha hopes that one day it will be possible to repair a damaged heart by sewing one of these patches over areas of muscle scarred by a heart attack.

Using advanced tissue-engineering techniques, researchers have already succeeded in creating replacement valves from the patients own tissue. This can be done by harvesting cells from elsewhere in the body (usually the blood vessels) and breeding them in a bioreactor, before seeding them on to a biodegradable polymer scaffold designed in the shape of a valve. Once the cells are in place they are allowed to proliferate before implantation, after which the scaffold melts away, leaving nothing but new tissue. The one major disadvantage of this approach is that each valve has to be tailor-made for a specific patient, a process that takes weeks. In the last couple of years, a group in Berlin has refined the process by tissue-engineering a valve and then stripping it of cellular material, leaving behind just the extracellular matrix the structure that holds the cells in position.

The end result is therefore not quite a valve, but a skeleton on which the body lays down new tissue. Valves manufactured in this way can be implanted, via catheter, in anybody; moreover, unlike conventional prosthetic devices, if the recipient is a child the new valve should grow with them.

If it is possible to tissue-engineer a valve, then why not an entire heart? For many researchers this has come to be the ultimate prize, and the idea is not necessarily as fanciful as it first appears.

In 2008, a team led by Doris Taylor, a scientist at the University of Minnesota, announced the creation of the worlds first bioartificial heart composed of both living and manufactured parts. They began by pumping detergents through hearts excised from rats. This removed all the cellular tissue from them, leaving a ghostly heart-shaped skeleton of extracellular matrix and connective fibre, which was used as a scaffold onto which cardiac or blood-vessel cells were seeded. The organ was then cultured in a bioreactor to encourage cell multiplication, with blood constantly perfused through the coronary arteries. After four days, it was possible to see the new tissue contracting, and after a week the heart was even capable of pumping blood though only 2% of its normal volume.

This was a brilliant achievement, but scaling the procedure up to generate a human-sized heart is made far more difficult by the much greater number of cells required. Surgeons in Heidelberg have since applied similar techniques to generate a human-sized cardiac scaffold covered in living tissue. The original heart came from a pig, and after it had been decellularised it was populated with human vascular cells and cardiac cells harvested from a newborn rat. After 10 days the walls of the organ had become lined with new myocardium which even showed signs of electrical activity. As a proof of concept, the experiment was a success, though after three weeks of culture the organ could neither contract nor pump blood.

Growing tissues and organs in a bioreactor is a laborious business, but recent improvements in 3D printing offer the tantalising possibility of manufacturing a new heart rapidly and to order. 3D printers work by breaking down a three-dimensional object into a series of thin, two-dimensional slices, which are laid down one on top of another. The technology has already been employed to manufacture complex engineering components out of metal or plastic, but it is now being used to generate tissues in the laboratory. To make an aortic valve, researchers at Cornell University took a pigs valve and X-rayed it in a high-resolution CT scanner. This gave them a precise map of its internal structure which could be used as a template. Using the data from the scan, the printer extruded thin jets of a hydrogel, a water-absorbent polymer that mimics natural tissue, gradually building up a duplicate of the pig valve layer by layer. This scaffold could then be seeded with living cells and incubated in the normal way.

Pushing the technology further, Adam Feinberg, a materials scientist at Carnegie Mellon University in Pittsburgh, recently succeeded in fabricating the first anatomically accurate 3D-printed heart. This facsimile was made of hydrogel and contained no tissue, but it did show a remarkable fidelity to the original organ. Since then, Feinberg has used natural proteins such as fibrin and collagen to 3D-print hearts. For many researchers in this field, a fully tissue-engineered heart is the ultimate prize.

We are left with several competing visions of the future. Within a few decades it is possible that we will be breeding transgenic pigs in vast sterile farms and harvesting their hearts to implant in sick patients. Or that new organs will be 3D-printed to order in factories, before being dispatched in drones to wherever they are needed. Or maybe an unexpected breakthrough in energy technology will make it possible to develop a fully implantable, permanent mechanical heart.

Whatever the future holds, it is worth reflecting on how much has been achieved in so little time. Speaking in 1902, six years after Ludwig Rehn became the first person to perform cardiac surgery, Harry Sherman remarked that the road to the heart is only two or three centimetres in a direct line, but it has taken surgery nearly 2,400 years to travel it. Overcoming centuries of cultural and medical prejudice required a degree of courage and vision still difficult to appreciate today. Even after that first step had been taken, another 50 years elapsed before surgeons began to make any real progress. Then, in a dizzying period of three decades, they learned how to open the heart, repair and even replace it. In most fields, an era of such fundamental discoveries happens only once if at all and it is unlikely that cardiac surgeons will ever again captivate the world as Christiaan Barnard and his colleagues did in 1967. But the history of heart surgery is littered with breakthroughs nobody saw coming, and as long as there are surgeons of talent and imagination, and a determination to do better for their patients, there is every chance that they will continue to surprise us.

Main photograph: Getty Images

This is an adapted extract from The Matter of the Heart by Thomas Morris, published by the Bodley Head

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Robot hearts: medicine's new frontier - The Guardian

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The American Heart Association (AHA) announced May 19 that it will donate two $1 million research grants to support research on medications and high blood pressure.

The money will be awarded over five years to Stanford University and the University of Pennsylvania, according to a statement from the AHA.

[These] competitive research programs are pushing the boundaries of their respective disciplines by undertaking high-risk projects whose outcomes could revolutionize the treatment for new classes of blood pressure medications and our approaches for clinical trials in the era of precision medicine, said Ivor Benjamin, MD, who chairs the AHAs research committee.

Joseph Wu, MD, the director of theStanford Cardiovascular Institute at Stanford University School of Medicine, is leading the research on medication. He plans to use information from stem cells to speed up the slow and expensive process of introducing a new drug to the market.

Our project has tremendous potential significance for testing new drugs very efficiently compared to the traditional drug screening that the pharmaceutical industry has to go througha process that has stagnated and become almost too costly to help patients, Wu said.

The second research project, spearheaded by Garret FitzGerald, MD, a professor of medicine and systems pharmacology and translational therapeutics at the University of Pennsylvanias Perelman School of Medicine, aims to improve blood pressure control over a 24-hour period.

Given the increasing prevalence of high blood pressure in our aging population and in the developing world generally, this program promises to have a considerable impact on global health, FitzGerald said.

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AHA awards $2 million to cardiac research at top universities - Cardiovascular Business

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After 20 years of trying, scientists have transformed mature cells into primordial blood cells that regenerate themselves and the components of blood. The work, described [May 17] in Nature offers hope to people with leukemia and other blood disorders who need bone-marrow transplants but cant find a compatible donor. If the findings translate into the clinic, these patients could receive lab-grown versions of their own healthy cells.

One team, led by stem-cell biologist George Daley of Boston Childrens Hospital in Massachusetts, created human cells that act like blood stem cells, although they are not identical to those found in nature. A second team, led by stem-cell biologist Shahin Rafii of Weill Cornell Medical College in New York City, turned mature cells from mice into fully fledged blood stem cells.

Time will determine which approach succeeds. But the latest advances have buoyed the spirits of researchers who have been frustrated by their inability to generate blood stem cells from iPS cells. A lot of people have become jaded, saying that these cells dont exist in nature and you cant just push them into becoming anything else, [Mick Bhatia, a stem-cell researcher at McMaster University, who was not involved with either study] says.

[Read the Daley study here.]

Read the Rafii study here.]

The GLP aggregated and excerpted this blog/article to reflect the diversity of news, opinion, and analysis. Read full, original post:Lab-grown blood stem cells produced at last

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Breakthrough for bone marrow transplant recipients: Lab-grown blood stem cells produced for first time - Genetic Literacy Project

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Q: How close are we to curing blood diseases with human stem cells?

A: New research has nudged scientists closer to one of regenerative medicine's holy grails: the ability to create customized human stem cells capable of forming blood that would be safe for patients.

Advances reported in the journal Nature could not only give scientists a window on what goes wrong in such blood cancers as leukemia, lymphoma and myeloma. They could also improve the treatment of those cancers, which affect some 1.2 million Americans.

While the use of blood-making stem cells in medicine has been common since the 1950s, it remains pretty crude. After patients with blood cancers have undergone powerful radiation and chemotherapy, they often need a bone-marrow transplant to rebuild their white blood cells, which are destroyed by that treatment.

The blood-making stem cells that reside in a donor's bone marrow and in umbilical cord blood harvested after a baby's birth are called "hematopoietic," and they can be life-saving. But even these stem cells can bear the distinctive immune system signatures of the person from whom they were harvested. So they can provoke an attack if the transplant recipient's body registers the cells as foreign.

This response, called graft-versus-host disease, affects as many as 70 percent of bone-marrow transplant recipients soon after treatment, and 40 percent develop a chronic version of the affliction later. It kills many patients.

Rather than hunt for a donor who's a perfect match, doctors would like to use a patient's own cells to engineer the hematopoietic stem cells.

The patient's mature cells would be "reprogrammed" to their most primitive form: stem cells capable of becoming virtually any kind of human cell. Then factors in their environment would coax them to become stem cells capable of giving rise to blood.Once reintroduced into the patient, the cells would take up residence without prompting rejection and set up a lifelong factory of healthy new blood cells.

If the risk of rejection could be eliminated, physicians might also feel more confident treating blood diseases that are not immediately deadly such as sickle cell disease and immunological disorders with stem cell transplants.

One of two research teams, led by stem cell pioneer Dr. George Q. Daley of Harvard Medical School and the Dana Farber Cancer Institute, started their experiment with human "pluripotent" stem cells primitive cells capable of becoming virtually any type of mature cell.

The scientists then programmed those pluripotent stem cells to become endothelial cells, which line the inside of certain blood vessels.Using suppositions gleaned from experiments with mice, Daley said his team confected a "special sauce" of proteins that sit on a cell's DNA and program its function. When they incubated the endothelial cells in the sauce, they began producing hematopioetic stem cells.

Daley's team then transferred the resulting blood-making stem cells into the bone marrow of mice to see if they would "take." In two out of five mice who got the most promising cell types, they did. Not only did the stem cells establish themselves, they continued to renew themselves while giving rise to a wide range of blood cells.

A second team, led by researchers from Weill Cornell Medicine's Ansary Stem Cell Institute, achieved a similar result using stem cells from the blood-vessel lining of adult mice.

But Daley cautioned that significant hurdles remain before studies like these will transform the treatment of blood diseases.

"We do know the resulting cells function like blood stem cells, but they still are at some distance, molecularly, from native stem cells," he said.

Melissa Healy, Los Angeles Times

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Medical Q&A: Progress made in getting stem cells to 'take' in mice - Sarasota Herald-Tribune

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Stem cell researchers at the University of Calgary have found another piece of the puzzle behind what may contribute to hair loss and prevent wounds from healing normally.

Jeff Biernaskies research, published recently in the scientific journal npj Regenerative Medicine identifies a key signalling protein called platelet-derived growth factor (PDGF). This protein is critical for driving self-renewal and proliferation of dermal stem cells that live in hair follicles and enable their unique ability to continuously regenerate and produce new hair.

This is the first study to identify the signals that influence hair follicle dermal stem cell function in your skin, says Biernaskie, an associate professor in comparative biology and experimental medicine at the University of Calgary'sFaculty of Veterinary Medicine, and Calgary Firefighters Burn Treatment Society Chair in Skin Regeneration and Wound Healing. Biernaskie is also a member of the Alberta Childrens Hospital Research Institute.

What we show is that in the absence of PDGF signalling hair follicle dermal stem cells are rapidly diminished because of their inability to generate new stem cells and produce sufficient numbers of mature dermal cells within the hair follicle.

Biernaskie and his team of researchers study dermal stem cells located within hair follicles. They are looking to better understand dermal stem cell function and find ways to use these cells to develop novel therapies for improved wound healing after injury, burns, disease or aging.

This study, co-authored byRaquel Gonzalez and Garrett Moffatt,shows that PDGF is key to maintaining a well-functioning stem cell population in skin. And in normal skin, if you dont have enough of it the stem cell pools start to shrink, meaning eventually the hair will no longer grow and wounds will not heal as well.

Its an important start in terms of how we might modulate these cells towards developing future therapies that could regenerate new dermal tissue or maintain hair growth says Biernaskie.

Biernaskies lab is looking at the potential role of stem cells in wound healing and the potential to stimulate these cells to improve skin regeneration, as opposed to forming scars.

The research is funded by a grant from Canadian Institutes for Health Research (CIHR) and the Calgary Firefighters Burn Treatment Society.

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UCalgary researchers identify 'signal' crucial to stem cell function in hair follicles - UCalgary News

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By 2027 to 2037 scientists will likely be able to create a baby from human skin cells that have been coaxed to grow into eggs and sperm and used to create embryos to implant in a womb.

The process, in vitro gametogenesis, or I.V.G., so far has been used only in mice. But stem cell biologists say it is only a matter of time before it could be used in human reproduction opening up mind-boggling possibilities.

With I.V.G., two men could have a baby that was biologically related to both of them, by using skin cells from one to make an egg that would be fertilized by sperm from the other. Women with fertility problems could have eggs made from their skin cells, rather than go through the lengthy and expensive process of stimulating their ovaries to retrieve their eggs.

IVF (Invitro fertilization) produces 70,000, or almost 2 percent, of the babies born in the United States each year. Worldwide there been more than 6.5 million babies born worldwide through I.V.F. and related technologies.

I.V.G. requires layers of complicated bioengineering. Scientists must first take adult skin cells other cells would work as well or better, but skin cells are the easiest to get and reprogram them to become embryonic stem cells capable of growing into different kinds of cells.

Then, the same kind of signaling factors that occur in nature are used to guide those stem cells to become eggs or sperm.

Last year, researchers in Japan, led by Katsuhiko Hayashi, used I.V.G. to make viable eggs from the skin cells of adult female mice, and produced embryos that were implanted into female mice, who then gave birth to healthy babies.

Nature Reconstitution in vitro of the entire cycle of the mouse female germ line

The female germ line undergoes a unique sequence of differentiation processes that confers totipotency to the egg. The reconstitution of these events in vitro using pluripotent stem cells is a key achievement in reproductive biology and regenerative medicine. Here we report successful reconstitution in vitro of the entire process of oogenesis from mouse pluripotent stem cells. Fully potent mature oocytes were generated in culture from embryonic stem cells and from induced pluripotent stem cells derived from both embryonic fibroblasts and adult tail tip fibroblasts. Moreover, pluripotent stem cell lines were re-derived from the eggs that were generated in vitro, thereby reconstituting the full female germline cycle in a dish. This culture system will provide a platform for elucidating the molecular mechanisms underlying totipotency and the production of oocytes of other mammalian species in culture.

Scientists could make an egg out of skin cells from women who cant produce viable eggsor who have other fertility problems, or who dont want to go through the difficult process of surgical removal of their eggs for IVF. Or men with fertility problems involving their sperm. Two women could make a child that was truly theirs, with eggs from one and sperm made from skin cells of the other. Or two men, vice-versa.

Mouse oocytes created from embryonic stem cells. Credit: Katsuhiko Hayashi, Kyushu Univ

In a couple of decades, Greely predicts, it will be possible to examine and select an embryo not just for a particular genetic disease but also for other traits, ranging from hair color to musical ability to potential temperament.

Greely concedes that Easy PGD will be mostly available in rich countries, but he also thinks it will be widely available in those countries because it will be free. Preventing the birth of people with genes that increase their risk of serious (and expensive) disease will save health care systems so much money that Easy PGD will be convincingly cost-effective.

That will be a powerful incentive to encourage prospective parents to further decouple procreation from sexual intercourse, and make it easy for them to drop off their skin cells at a lab. The lab will then generate a big supply of embryos containing the couples genes, embryos that can be examined for desirable characteristics as well as disease genes. The winner of this elimination contest will, presumably, be selected for implantation.

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Mice embryos from skin cells and by 2037 human embryos from skin cells - Next Big Future

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BENGALURU:Full-fledged treatment for cancer and bone-related ailments using stem-cell within the state could soon be a possibility if a plan of a world renowned surgeon from the state succeeds.

Dr A A Shetty is a highly decorated orthopedic surgeon and professor based in the UK who won the Nobel equivalent of surgery called the Hunterian Medal, this year. In his aim to bring about next level cancer and orthopedic treatment, he has already set up two big stem cell research labs - one in Dharwad and another in Mangaluru, a few years back at a cost of around 20 to 25 crore. A hospital that will treat stem-related ailments has also been envisaged at a total cost of around Rs 200 to 250 crore.

Setting up the labs is part of a three-step goal. After setting up the labs, the next step will be producing the stem cells, whether it be for bone ailments, treatment for cervical cancer etc. Then the third step will be the application of these stem cells through our hospital or through tie-ups with other hospitals. I have already received the funding for setting up the hospital, says Dr Shetty in an interaction with CE in Bengaluru. He is originally from a small village called Asode in Udupi district.

The lab in Dharwad is located at SDM College and is being backed by Shri Dharmasthala Manjunatheshwara and will be primarily working on blood cancer and thalassemia treatment. The one in Mangaluru is located at K.S. Hegde Medical Academy (KSHEMA) and is backed by the NITTE group. It will work on cartilage and bone fracture treatments.The effort is no doubt for profit. We will charge the rich but the poor will be treated for free at our hospital, he says.

Already, Shetty has recruited a number of top stem cell researchers from the state who are presently abroad. I have recruited researchers who were doing their postdoc studies in Japan, South Korea. Presently there are four of them working at the two labs, he says. Shetty ultimately wants to settle in Karnataka and hopes to achieve his goal by 2020. The third stage of his plan also requires expertise in various cutting edge technologies such as robotics, computing and he will also be recruiting people who specialize in these fields.

Cancer Vaccination

Shetty also hopes to make cancer vaccination a possibility. Giving an example of cervical cancer, Shetty says, Few cancers can be vaccinated. Cervical cancer, one of the most rampant cancers, is one of them. We will use stems derived from iPS cell. In the UK, the vaccine cost 60 pounds. Our aim is to develop it and sell it at a very low cost, as low as Rs 100, he adds. Induced Pluripotent Stem Cells or iPS Cells are derived from the blood and skiwwn cells and can be reprogrammed to provide an unlimited source of any type of human cell.

Stem cells for Arthritis In 2013, Shetty devised a minimally invasive procedure to treat arthritis using stem cells. When the cartilage between the bones begin to erode, the bones rub against each other and cause severe pain. Shetty treated a patient suffering from knee arthritis. He drilled a hole into the patients knee bone and released stem cells that could grow into the cartilage. In all, the procedure lasted just 30 minutes. Shetty has already done as many as two dozen such procedures in India.

Trauma Center Shetty also says that he wants to develop and provide integrated trauma services. If a patient survives the golden hour then he/she can be saved. Majority die in the first hour of trauma. My integrated services will have specialized suits that will help reduce blood loss and will have other know-how. I am negotiating with the International Rotary on this, he adds. This may be established either in Mangalore or Bangalore.

Dr Vishal Rao, head and neck oncology surgeon at HCG Hospitals says that stem cells research is in the mid-stage of development and has great potential to grow in India. The IT and BT ministry is already taking great steps by encouraging startups on these lines, starting various schemes, he says. Vishal also pointed out that a number of private organizations, hospitals and individuals like those like Dr Shetty are also investing in the field.

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Stem-cell therapy for cancer comes closer home - The New Indian Express

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News

Published online 22 May 2017

Two teams of Arab and American researchers are tantalizingly close to generating primordial blood stem cells in the lab.

Louise Sarant

Hematopoietic stem and progenitor cells (HSPC) from human iPS cells. Rio Sugimura Two teams of scientists have developed methods that make lab-grown blood stem cells a realistic prospect a goal for hematology researchers since human embryonic stem (ES) cells were first isolated in 1998.

Scientists have previously succeeded in genetically reprogramming skin cells to make pluripotent stem (iPS) cells, which are later used to generate multiple human cell types. However, the ability to induce blood stem cells that self-regenerate, for the treatment of millions affected by blood cancers and genetic disorders, has eluded researchers.

The two papers newly published in Nature describe methods that pave the way for safe, artificial and bona fide hematopoietic stem cells (HSCs) generation. Hematopoietic stem (HSC) cells are the common ancestor of all cells created in the body, producing billions of blood cells every day.

This bears major implications for cell therapy, drug screening and leukemia research. The root causes of blood diseases can be scrutinized and creating immune-matched blood cells, derived from a patients own cells, is now conceivable.

The first team, based at the Boston Childrens Hospital, has generated blood-forming stem cells (HSCs) in the lab using pluripotent stem cells for the first time.

Were tantalizingly close to generating bona fide human blood stem cells in a dish, says senior investigator George Daley, who heads the research lab in Boston Childrens Hospitals stem cell program and who is dean of Harvard Medical School. This work is the culmination of over 20 years of striving.

Ryohichi Rio Sugimura, the studys first author and a postdoctoral fellow in the Daley Lab, says his team exposed human pluripotent stem cells (both ES and iPS cells) to chemical signals to prompt them to differentiate into specialized cells and tissues during embryonic development.

"Sugimura and his colleagues delivered transcription factors proteins that control and regulate the transcription of specific genes into the cells using a lentivirus, a vector to deliver genes. The resultant cells were transplanted to immune deficient mice, where human blood and immune cells were made, he says.

A few weeks after the transplant, a small number of rodents were found to be carrying multiple types of blood cells in their bone marrow and blood; cells that are also found in human blood. This is a major step forward for our ability to investigate genetic blood disease, says Daley.

The second team, a group of scientists from Weill Cornell Qatar and Weill Cornell Medicine in New York, used mature mouse endothelial cells cells that line blood vessels as their starting material for generating HSCs.

Image of human CD45+ blood cells differentiated from iPS cells. Rio Sugimura Based on previous work, we hypothesized that endothelial cells are the mastermind of organ development, explains Jeremie Arash Rafii Tabrizi, paper co-author and researcher at the stem cell and microenvironment laboratory at Weill Cornell Medicine, Qatar.

The team isolated the cells, and then pushed key transcription factors into their genomes. Between days 8 and 20 into the process, the cells specified and multiplied.

Our research showed that endothelial cells can be converted into competent HSCs with the ability to both regenerate the myeloid and lymphoid lineage, he explains.

The method brings hope for people afflicted with leukemia requiring HSCs transplantation, or genetic disorders affecting the myeloid or lymphoid lineages. The clinical generation of HSCs, derived from the same individual, can eventually help scientists correct genetic abnormalities.

As exciting as the two studies are, rigorous tests are still required to check the normality of lab-grown cells before the clinical phase, says Alexander Medvinsky, professor of hematopoietic stem cell biology at the University of Edinburgh Medical Research Council Centre for Regenerative Medicine. Medvinsky was not involved in either study.

The risks of infusion of genetically engineered cells in humans should not be underestimated, he weighs in. Tests and trials to generate safe fully functional human blood stem cells may take many years, in contrast to similar assessment in short-living mice. It is not clear now whether blood stem cells can become cancerous in the longer term.

He adds however that this type of research is exactly what is required to potentially meet clinical needs.

doi:10.1038/nmiddleeast.2017.89

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Lab-grown blood stem cells - Nature Middle East

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The recent emergence of easily accessible CRISPR-Cas9 technologies is enabling nearly unlimited opportunities for genome editing. Apart from its potential as a therapeutic tool, the system is currently spurring a revolution in drug discovery.

The targets were finding with CRISPR-Cas9 are going to guide the drugs coming out in the 2020s, said Jon Moore, CSO of Horizon Discovery, at a recent event in the UK. Only shortly after the first publication on the new genome engineering system in late 2012, the gene editing company and CRO started to recognize the potential of the new technology.

Around 2013 we started getting interested in CRISPR-Cas9 () and over the next year and a half we went from predominantly generating models using AAV to almost exclusively using CRISPR-Cas9,Chris Lowe, Head of Research Operations at Horizon, told us. Today, the company uses CRISPR across all of its platforms from engineering customized cell lines or animal models to performing functional screens. We can generate hundreds of knock-outmodels a month on a rolling platform. And thats really only possible because of the CRISPR-Cas9 technology. Its pretty much all pervasive, commented Chris.

To date, most of the attention on CRISPR has revolved around its potential as a therapeutic tool and the possibilities of engineering human embryos, crops or life stock. However, it seems like the real revolution right now is taking place in the lab. In 2015 alone, the scientific community published 1,185 publications (corresponding to 3 publications a day!) on the new gene editing system, and scientists have hacked the system to do far more than just cut DNA. CRISPR appears to be emerging as a key tool for drug discovery ranging from target identification and validation to preclinical testing.

RNA-guided Cas9 nucleases, which are derived from microbial adaptive immune systems, are enabling fast and accurate alterations of genomic information in mammalian model systems, including human tissues. While genome editing tools are not entirely new, Chris told us that the benefit of CRISPR really is in the speed and ease with which you can create the reagents necessary to perform gene editing, thereby overcoming many limitations of its predecessors such as zinc-finger nucleases (ZFN) and transcription activator-like effector nucleases (TALENs).

Cas9 makescuts at specific locations along the DNA with help from a short stretch of guide RNA that targets the Cas9 endonuclease to a specific site. By simply changing the guide RNA sequence, Cas9 can be directed to any site within the genome. The synthesis of such short pieces of RNA is way simpler than having to engineer a whole protein to direct it towards a specific DNA sequence.

The resulting double-strand break is then repaired by the cells error-prone DNA repair machinery. That alone is usually enough to knock-out the gene of interest and allows scientists to study what happens to cells or organisms when the protein or gene is shut off. Alternatively, the scientist can provide a piece of new DNA, maybe a new gene, which is then built in at the target site.

The RNA-guided Cas9 nuclease.

CRISPR gives scientists the opportunity to engineer and study virtually all cell types and it has become common practice around the globe. In fact, as the system is incredibly fast and cost-effective, it has enabled scientists, for the first time, to conduct high-throughput knock-out screens to speed up target discovery.

Using retroviral libraries of guide RNAs that target every single gene within the genome, CRISPR can be used to generate thousands of different cell lines at once, each containing a different guide RNA that targets a particular gene.

Principle setup of a CRISPR screen.

Feng Zhangs lab, the first lab that used CRISPR to engineer human cells, made use of such genome-wide screens to address treatment resistance to melanoma. BRAF V600E is a common cancer mutation that is treated by the FDAapproved drug vemurafenib. Yet, the rapidly mutating cancer cells quickly become resistant, and by 24 weeks of treatment, the tumors return.

We thought this might be an opportunity for us to apply a genome-scale library to see what are the geneswhen you either turn them on or turn them offthat would render the tumor cell resistant to vemurafenib, Zhang explained in an article in The Scientist.

Apart from identifying genes that make cells resistant to specific drugs, researchers are using the system toscreen for genes that are essential to the cancer cells, but not normal cells a state referred to assynthetic lethality. Others are using CRISPR screens to search for survival factors of pathogens such as the Zika and Dengue viruses.

Although RNA interference-based screens were widely used beforeCRISPR, the new system has considerable advantages.Most significantly, gene editing will lead to the complete inactivation of a target, compared to the incomplete knockdown seen with RNA interference (RNAi). In addition, confounding off-target effects of siRNA molecules are widely reported. As Chris told us, we are seeingmuch greater reproducibility than what weve seen using RNAi over the years. So thats a big element thats driving the adoption of the CRISPRscreening technique as a complementary technique to the siRNA approaches.

A key to successful drug development isthe availability of suitable model systems to make early drug development decisions. As Friedhelm Bladt, Director of Biomarker Strategy at Bayer, told us, One limitation in drug development is that you test your efficacy in mouse models, sometimes in rats. But these animals react very differently from a human being and they are in some aspects much more robust than human beings would be.

Generating a new disease model used to be a laborious and expensive tasklimited to a few species that came with a good tool kit for genetic manipulation. CRISPR now allows us to generate much better animal models that really reflect the human situation,commented Friedhelm.

Today, CRISPR has been used to engineer a wide range of species including rats, dogs and cynomolgous monkeys, which are all commonly used during preclinical drug discovery. Others are using it to engineer the genome of ferrets, in order to modify their susceptibility to flu infections. These animals are much better suited as influenza transmission models, due to the fact that unlike mice, ferrets sneeze when infected.

Another major advantage is that CRISPR allows tweaking more than one gene at a time, taking into account that most human diseases are not monogenic. Tumors, for example, are very heterogeneous and you usually have a lot of different types of mutations as well asdifferences within thetumor. Modeling that is a huge challenge in animal models, explained Friedhelm. With CRISPR we are able to really introduce aset of mutations or potentially even introduce some heterogeneity in thetumors.

Creating a mouse model with multiple mutations used to take years due to lenghty backcrossing, costing about $20,000 per mutation. With CRISPR, this time has been reduced to months or even weeks.

Apart from serving as a gene editing tool, CRISPR has already been hacked to do much more than that. As Chris explained: I see the CRISPR system not so much as an editing tool but more as a targeting system. It allows us to precisely target tools to specific locations in the genome and this ability is challenging our imagination, allowing the investigation of much more subtle effects on the genome compared to the fairly blunt technique that was brought out a couple of years ago where you just damage the DNA and let it repair.

When the group of Jonathan Weissman at the University of California, San Francisco (UCSF) got hold of CRISPR, the first thing they did was to break the scissors, he explains in a recent Natureinterview. The group mutated the Cas9 protein so that it still bound to the DNA but no longer cut it, allowing the team to turn off genes without changing the DNA sequence.

Then they tethered Cas9 to a protein that activates gene expression. They now had a simple system available that allowed them to turn genes either on or off at their will. Others are using CRISPR to make more subtle modifications to the DNA: by coupling CRISPR to epigenetic modifiers such as histone acetylases, scientists are able to study the direct effect of epigenetic marks, providing a straightforward tool to study how epigenetics can drive disease. These types of alterations can be modified with CRISPR in a much more selective way than it was possible in the past, explained Friedhelm. And there are many more potential applications people have just started to discover these.

Since its appearance in 2012, CRISPR has given rise to a massive number of new tools that are impacting the entire drug discovery process. The system is redefining whats possible in R&D, which is why many biotech and pharma companies have started integrating the technology into their R&D programs.

Novartis recently entered a partnership with Jennifer Doudnas Caribou Biosciences to accessCaribous CRISPR drug screening and validation technologies, while AstraZeneca signed up for four research collaborations to use CRISPR across its entire drug discovery platform. Similarly, German Evotec recently teamed up with Merck to access its CRISPR libraries that are based on a license from the Broad Institute.

As CRISPR Therapeutics CEO Rodger Novak told us at our last Refresh Event, There is probably no larger biotech or pharma company out there anymore, who have their own R&D, who are not using CRISPR. They are all using CRISPR in their labs. Its a very powerful technology, not only for human therapeutics.

Images via shutterstock.com / CHORNYI SERHII / Perception7 / unoL; horizondiscovery.com; igem.org

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How the CRISPR-Cas9 System is Redefining Drug Discovery - Labiotech.eu (blog)

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Sacramento Bee

Will this gene-editing tool cure the diseases of the future? Sacramento Bee The most used gene-editing agent is CRISPR-cas 9, a combination of an enzyme that cuts strands of DNA at a specific location and a predesigned RNA sequence that binds to the DNA. Usually, a professionally trained microinjectionist delivers CRISPR-cas9 ...

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Will this gene-editing tool cure the diseases of the future? - Sacramento Bee

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Denver, Colo., May 23, 2017 / 03:04 am (CNA/EWTN News).- With plans for the first human head transplant surgery looming in the next year, a lead doctor on the formidable project has high hopes for the procedure.

Along with the aim of finding a new body for a yet-to-be-selected patient, the physician says that the surgery as a first step toward immortality will effectively disprove religion.

But Catholic critics have called into question not only the ethics of such a risky procedure, but the dubious claim that such a development would render belief in God irrelevant.

The actual trying of the surgery at this point I think would be unethical because of the tremendous risk involved, and it is an unproven surgery, Dr. Paul Scherz, assistant professor of moral theology and ethics at The Catholic University of America, told CNA.

Sherz made his remarks following the news that Italian doctor Sergio Canavero is aiming to carry out the first human head transplant surgery within the next 10 months. Its a process Canavero hopes will pave the way for the process of transplanting cryogenically frozen brains and ultimately, in his view, to the eradication of death.

Canavero serves as director of Turin Advanced Neuromodulation Group and has teamed up with Harbin Medical Centre and Doctor Xiaoping Ren, an orthopedic surgeon who was involved with the first successful hand transplant in the U.S. The first surgical attempt for the head transplant is expected to take place in China, where the group says theyre more likely to find a donor body.

Cryonics involves the freezing of the brain or even the whole body of patients, with expectations that future science will have the means to restore the frozen tissue and extend life.

Because conscious minds will have experienced life outside of death, Canavero said the surgery would then remove the fear of death and the peoples need for religion. He said if the process succeeds, religions will be swept away forever.

However, Sherz responded that even if the surgery was a success, it would not disprove the Catholic faith.

There is nothing in the Catholic tradition of how we understand the soul that would think that if you moved a head or moved the brain that that wouldnt allow the person to come back to life, he said.

Turin Advanced Neuromodulation Group has already claimed that a successful head transplant has been carried out on a monkey, but not all scientists agree that the operation can be recorded as a success.

Before the monkeys head was stitched back together, it was removed, cooled, and the blood of the transplant body was cross circulated with an outside source. Canavero and his group claimed the supply of blood was then connected to prove the surgery succeeded without brain damage, but the spinal cord was left unattached.

How the connected blood supply proves the surgery is possible without brain damage was not described, and many bioethicists are skeptical of the publication of the surgerys success without proper peer review and of the issues around the severed spine.

Because the technology has not yet been developed, the bioethicists worry that the severed spine may never be reconstructed, leaving the patient worse off than before.

Despite the pervasive belief in the surgerys failure, Canavero claims theres a 90 percent chance that the human head transplant will succeed. And not only that, its success would allow humans to no longer need to be afraid of death.

Father Tad Pacholczyk, who serves as a bioethicist for the National Catholic Bioethics Center, disagreed with Canaveros definition of being brought back to life.

He said to assume death as a necessary product of either the head surgery or brain surgery is gullible and mistaken, as there is potential for the patient to be merely unconscious.

The patient undergoing the head transplant is not dead, only unconscious, he told CNA. There is not any bringing back to lifeThere is merely a restoration of consciousness, briefly lost during the movement of the head from one human body to the other.

Scherz also said that the Church accepts an intimate and mysterious relationship between soul and body, and that the procedures success wouldnt necessary disprove the soul or religion.

Our neurological tissue has important part to play in our soulThe soul is always intimately related to the body. We are not just souls that are disembodied, right? We are embodied spirits or spirited bodies.

Most physicians agree that the proposed surgerys success rate is infinitesimal, and theyve questioned the morality of a procedure thats doomed to fail and the unrealistic hope life extension projects could give to people.

I am concerned that the rights of vulnerable patients undergoing cryonics cannot be protected indefinitely, Dr. Channa Jayasena, a lecturer in Reproductive Endocrinology at Imperial College in London, told the Telegraph.

Cryonics, she said, has risks for the patient, poses ethical issues for society, is highly expensive, but has no proven benefit.

And the hope for immortal life, Scherz weighed in, isnt a realistic desire in a fallen world. Living forever in bodily form is not going to satisfy anyone, he said.

If the goal is not to help someone to get back bodily movement or things like that, but to try to live forever on this earth, then I think if you really want to get over the fear of death then you will have to come to terms with the fact that we are mortal.

That whats going to help you to live a better life because you are going to be willing to give your life to things like service.

In fact, he said that people in transhumanist movements have admitted they would most likely avoid risky behavior in order to preserve their lives.

If life extension projects come into being there is so much more to lose and you committed yourself to trying to live on this earth for as long as possible, which stands in contrast to the Catholic tradition and a lot of the philosophical traditions, Scherz noted.

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Why Head Transplants Won't Disprove the Existence of God - Patheos (blog)

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INTRODUCTION

Treatment of patients with hypopituitarism is the sum of the treatments of each of the individual pituitary hormonal deficiencies detected when a patient with a pituitary or hypothalamic disease is tested. The treatments of corticotropin (ACTH), thyroid-stimulating hormone (TSH), and luteinizing hormone (LH) and follicle-stimulating hormone (FSH) deficiencies are in many ways the same as the treatments of primary deficiencies of the respective target glands, but in other ways they differ. Both the similarities and differences will be highlighted below. Treatment of growth hormone (GH) deficiency is unique to hypopituitarism.

The specifics of therapy for hypopituitarism will be reviewed here. The causes, clinical manifestations, and diagnosis of hypopituitarism, as well as GH deficiency in adults and the management of individual hormone deficiencies, are reviewed in more detail elsewhere. (See "Causes of hypopituitarism" and "Clinical manifestations of hypopituitarism" and "Diagnostic testing for hypopituitarism" and "Growth hormone deficiency in adults".)

IMPORTANCE OF TREATMENT

One reason to optimize treatment is that in a retrospective study of 344 patients who had hypopituitarism after pituitary surgery, the long-term mortality was about double that of the general population [1]. Most of the excess mortality was due to cerebrovascular disease. The relationship between the hypopituitarism and the excess mortality remains unknown, and we do not know if even optimal treatment will improve mortality.

ACTH DEFICIENCY

The primary consequence of lack of corticotropin (ACTH) is cortisol deficiency. As a result, treatment consists of the administration of hydrocortisone or other glucocorticoid in an amount and timing to mimic the normal pattern of cortisol secretion. Because there is no test to assess the adequacy of the replacement, the optimal replacement glucocorticoid and the optimal doses are not known. Most authorities recommend replacement with hydrocortisone because that is the hormone the adrenal glands make normally, but others prefer prednisone or dexamethasone for their longer durations of action.

Preparation and doseMost authorities recommend hydrocortisone doses of 15 to 25 mg/day [2,3] because those doses are similar to daily production rates [4]. Patients who are more severely deficient or weigh more tend to need doses at the upper end of this range and vice versa. Some patients, however, need even larger doses to avoid severely symptomatic adrenal insufficiency, and others can get by on smaller amounts.

Literature review current through: Apr 2017. | This topic last updated: Nov 03, 2015.

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Treatment of hypopituitarism - uptodate.com

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Amy Neff Roth

Dominic Tebo has gotten a lot of love and a lot of medical care in his young life.

The Clinton 2-year old was born with an array of medical problems and has undergone many treatments. His parents put the other parts of their lives on hold for six months so they could stay in Syracuse while he remained in the neonatal intensive care unit.

Now Dominic needs one thing his parents cant afford to give him an accessible home.

My child has love. He has toys. He has everything that a 2-year-old needs, a normal two-year old. But unfortunately, I cannot give him the room to keep progressing, said Dominics mother, Monica Moffo.

So the Lake Delta Kiwanis are stepping in, hosting a fundraiser Sunday in Lee Center to raise money for the family. It will take place from noon to 5 p.m. at the Lee Center Fire Hall at 5510 School St. It will feature a chicken barbecue, live music and 50/50 and gift basket raffles. The cost is $10 per person.

Moffo and her fianc, Eric Tebo, Dominics father, lived in Lee Center before they temporarily stopped working to be with Dominic. Now they live in Clinton with Moffos mother.

Dominic has a rare gene mutation known as MAG-2. His doctor told the family that hes one of only five people in the world and the only one in the United States known to have the condition, Moffo said. Its rarity is apparent in the lack of information available through a Google search.

He has all his chromosomes and out of one of his chromosomes theres thousands of letters in a chromosome out of all of his chromosomes, hes missing one letter, Moffo explained.

Moffo said theyve been told that all the people with the mutation have respiratory problems like Dominic. But Dominic was born with a laundry list of medical conditions, many of which the others do not have, Moffo said.

Dominic was born with hypopituitarism (malfunctioning of the pituitary gland), tracheomalachia (in which the cartilage is so soft that the trachea partially collapses), clench hands, club feet, bell-shaped lungs and an enlarged tongue. He has a tracheotomy to help his breathing and had surgery on his tongue a year and a half ago. He used to be on a feeding tube, but hes able to eat on his own now.

Hes had multiple surgeries, some life threatening, and has been in and out of the hospital. Hes about to scooch around the house now and is learning to use a walker, his mother said. He also has a weakened immune system so his family tried to keep him somewhat isolated.

Its not clear if all his problems are linked to his genetic defect or if he has another medical condition as well.

They literally consider him an open book mystery, Moffo said.

Despite the challenges, Dominic has come a long way, she said.

Hes a very happy boy, she said, and always a smile, no matter what.

Follow @OD_Roth on Twitter or call her at 315-691-2961

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Clinton child battles rare genetic disorder - Utica Observer Dispatch

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