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

Skin Stem Cells Comments Off on ‘Signal’ Crucial to Stem Cell Function in Hair Follicles Identified – Technology Networks | May 24th, 2017

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.

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

Skin Stem Cells Comments Off on Trendy Skin Care Ingredients Are Being Added to Hair Care Products – Allure Magazine | May 24th, 2017

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Conservative Reps Urge Trump to Fire NIH Head - WMGT 41 NBC News Stem Cell Research.Experimenting with cells in petri dish by adding fluid from a pipette, used in therapeutic cloning, microbiology, genetic engineering an. and more »

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Conservative Reps Urge Trump to Fire NIH Head - WMGT - 41 NBC News

Spinal Cord Stem Cells Comments Off on Conservative Reps Urge Trump to Fire NIH Head – WMGT – 41 NBC News | May 23rd, 2017

May 23, 2017

Researchers from the University of Basel in Switzerland have identified a key regulator gene for the formation of cardiac valves - a process crucial to normal embryonic heart development. These results are published in the journal Cell Reports today.

The heart is the first functional organ that develops in vertebrate embryos. In humans, it starts to beat four weeks into the pregnancy. Unfortunately, congenital heart disease is one of the most common developmental abnormalities and the leading cause of birth defect-related deaths. These heart defects often involve malformations of cardiac valves, which are required to regulate the pressure and flow of blood in the cardiac chambers.

Unexpected role for HAND2 transcription factor in cardiac valve formation

A research team led by Prof. Zeller and Dr. Zuniga from the University of Basel has identified the so-called HAND2 gene as a key regulator that triggers the formation of cardiac valves in mouse embryos, a process that is crucial for normal heart development. Previous research using mouse models lacking HAND2 had shown that this gene regulates outflow tract and right ventricle development.

The researchers thus set out to identify the set of genes that are controlled by HAND2 in developing mouse hearts. In doing so, they identified a previously unknown heart defect in mouse embryos lacking HAND2. The mutant hearts lack the cardiac cushions, which would normally develop into cardiac valves. Normally, the cells contributing to these cushions undergo complex cellular rearrangements as they detach from the lining of the heart wall and migrate into the cushions to "fill them up". As this mechanism is crucial for heart development, the researchers investigated how HAND2 controls this fundamental event during cardiac valve development.

HAND2 controlled gene network

In humans, defects in valve formation underlie different congenital heart malformations but the molecular mechanisms controlling heart valve development are not well understood. By studying mouse embryos, the research group has now identified the network of genes directly controlled by HAND2 that regulates cardiac valve formation.

The discovery of the HAND2 controlled gene network is of general relevance as mutations in HAND2 have recently been linked to heart valve malformations in human patients. «Not only does this discovery advance our molecular knowledge of cardiac valve development, but it may also help to provide genetic diagnosis for patients that suffer from congenital heart malformations," says first author Frderic Laurent of the Department of Biomedicine.

Engineering valves from stem cells

Heart valve replacements are among the most common cardiac surgeries performed and one of the future promises of biomedical research is to engineer replacement valves from stem cells. The discovery that HAND2 is a key regulator of the cellular and gene regulatory processes underlying heart valve formation is a potential milestone in this direction.

Explore further: Scientists get the upperhand in biological pathway that leads to heart formation

More information: Frdric Laurent, Ausra Girdziusaite, Julie Gamart, Iros Barozzi, Marco Osterwalder, Jennifer A. Akiyama, Joy Lincoln, Javier Lopez-Rios, Axel Visel, Aime Zuniga, and Rolf Zeller, HAND2 Target Gene Regulatory Networks Control Atrioventricular Canal and Cardiac Valve Development, Cell Reports 19 (2017) DOI: 10.1016/j.celrep.2017.05.004

Journal reference: Cell Reports

Provided by: University of Basel

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Researchers at the Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC) have demonstrated the crucial role of the NOTCH signaling pathway in the development of a fundamental heart structure, the heart valves. ...

Heart valve defects are a common cause of death in newborns. Scientists at the University of Bonn and the caesar research center have discovered "Creld1" is a key gene for the development of heart valves in mice. The researchers ...

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May 5, 2016A cell-to-cell signaling network that serves as a developmental timer could provide a framework for better understanding the mechanisms underlying human heart valve disease, say University of Oregon scientists.

The first known identification of two genes responsible for hypoplastic left heart syndrome (HLHS), a severe congenital heart defect, has been reported by researchers at the University of Pittsburgh School of Medicine. The ...

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A new gene behind a rare form of inherited childhood kidney disease has been identified by a global research team.

In the earliest stages of embryonic development, a protein known as TET1 may be the factor that tips the balance toward health or disease. The first evidence for this vital role of TET1 is presented in Nature Genetics by ...

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Discovery of a key regulatory gene in cardiac valve formation - Medical Xpress

Cardiac Stem Cells Comments Off on Discovery of a key regulatory gene in cardiac valve formation – Medical Xpress | May 23rd, 2017

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

Cardiac Stem Cells Comments Off on Robot hearts: medicine’s new frontier – The Guardian | May 23rd, 2017

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)

Cardiac Stem Cells Comments Off on Miltenyi Biotec Showcases the Generation of Purified Human iPSC Derived Cardiomyocytes – PR Web (press release) | May 23rd, 2017

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

Cardiac Stem Cells Comments Off on AHA awards $2 million to cardiac research at top universities – Cardiovascular Business | May 23rd, 2017

Currently, there are only 11 hospitals that are authorized to give stem cell treatments in Indonesia. (Shutterstock/File)

Developments in science and technology have enabled humankind to achieve the unthinkable, including advancements in healthcare. In the next 10 years, patients may not even need medicine to cure certain illnesses as reported by kompas.com.

Principal investigator of Stem Cell and Cancer Institute, Dr. Yuyus Kusnadi, said health scientists are developing stem cell treatments. Stem cells are cells with the ability to renew or regenerate any kind of cells.

Degenerative conditions such as kidney failure and the weakening of heart muscles in the future may be cured by injecting stem cells into the patients body.

Stem cells can be obtained from umbilical cord blood that is kept in a stem cell bank, back bone marrow and fat. However, fat and bone marrow will decline in quality as a person grows older. Stem cells stored in a stem cell bank can be used for future treatments if needed.

Read also: Scientists take first steps to growing human organs in pigs

Health treatments using stem cells exist today although they are not yet developed due to limitations in funding and technology. Yuyus said in Indonesia, those who are allowed stem cell treatment are those who have no option.

For now, stem cell treatment require a doctors approval. Its still subjective, he said.

For those with recommendations for stem cell treatment, the stem cell is obtained from blood or fat. Manipulation in the laboratory is needed to strengthen the stem cell.

Although stem cell treatments are not yet popular these days, Yuyus is optimistic, Lets wait five to ten more years. The current use of medicine only stops symptoms and does not fix the sickness, he said.

Stem cell treatments will not be cheap either, as it will cost patients up to hundreds of millions of rupiah.

Currently, there are only 11 hospitals that are authorized to give stem cell treatments in Indonesia. The hospitals right to provide stem cell treatments is regulated in the Health Ministers Regulation no. 32, 2014 on the Incorporation of Medical Research Service and Education of Tissue and Stem Cell Centers.

Hospitals authorized to provide stem cell treatments in Indonesia include Rumah Sakit Cipto Mangun Kusumo, RS. Sutomo, RS M. Djamil, RS. Persahabatan, RS. Fatmawati, RS. Dharmais, RS. Harapan Kita, RS. Hasan Sadikin, RS. Kariadi, RS. Sardjito and RS. Sanglah. (asw)

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Stem cell treatments ready to replace medicine in 10 years: Expert - Jakarta Post

Bone Marrow Stem Cells Comments Off on Stem cell treatments ready to replace medicine in 10 years: Expert – Jakarta Post | May 23rd, 2017

knowledge center home stem cell research all about stem cells what are stem cells?

Stem cells are a class of undifferentiated cells that are able to differentiate into specialized cell types. Commonly, stem cells come from two main sources:

Both types are generally characterized by their potency, or potential to differentiate into different cell types (such as skin, muscle, bone, etc.).

Adult or somatic stem cells exist throughout the body after embryonic development and are found inside of different types of tissue. These stem cells have been found in tissues such as the brain, bone marrow, blood, blood vessels, skeletal muscles, skin, and the liver. They remain in a quiescent or non-dividing state for years until activated by disease or tissue injury.

Adult stem cells can divide or self-renew indefinitely, enabling them to generate a range of cell types from the originating organ or even regenerate the entire original organ. It is generally thought that adult stem cells are limited in their ability to differentiate based on their tissue of origin, but there is some evidence to suggest that they can differentiate to become other cell types.

Embryonic stem cells are derived from a four- or five-day-old human embryo that is in the blastocyst phase of development. The embryos are usually extras that have been created in IVF (in vitro fertilization) clinics where several eggs are fertilized in a test tube, but only one is implanted into a woman.

Sexual reproduction begins when a male's sperm fertilizes a female's ovum (egg) to form a single cell called a zygote. The single zygote cell then begins a series of divisions, forming 2, 4, 8, 16 cells, etc. After four to six days - before implantation in the uterus - this mass of cells is called a blastocyst. The blastocyst consists of an inner cell mass (embryoblast) and an outer cell mass (trophoblast). The outer cell mass becomes part of the placenta, and the inner cell mass is the group of cells that will differentiate to become all the structures of an adult organism. This latter mass is the source of embryonic stem cells - totipotent cells (cells with total potential to develop into any cell in the body).

In a normal pregnancy, the blastocyst stage continues until implantation of the embryo in the uterus, at which point the embryo is referred to as a fetus. This usually occurs by the end of the 10th week of gestation after all major organs of the body have been created.

However, when extracting embryonic stem cells, the blastocyst stage signals when to isolate stem cells by placing the "inner cell mass" of the blastocyst into a culture dish containing a nutrient-rich broth. Lacking the necessary stimulation to differentiate, they begin to divide and replicate while maintaining their ability to become any cell type in the human body. Eventually, these undifferentiated cells can be stimulated to create specialized cells.

Stem cells are either extracted from adult tissue or from a dividing zygote in a culture dish. Once extracted, scientists place the cells in a controlled culture that prohibits them from further specializing or differentiating but usually allows them to divide and replicate. The process of growing large numbers of embryonic stem cells has been easier than growing large numbers of adult stem cells, but progress is being made for both cell types.

Once stem cells have been allowed to divide and propagate in a controlled culture, the collection of healthy, dividing, and undifferentiated cells is called a stem cell line. These stem cell lines are subsequently managed and shared among researchers. Once under control, the stem cells can be stimulated to specialize as directed by a researcher - a process known as directed differentiation. Embryonic stem cells are able to differentiate into more cell types than adult stem cells.

Stem cells are categorized by their potential to differentiate into other types of cells. Embryonic stem cells are the most potent since they must become every type of cell in the body. The full classification includes:

Embryonic stem cells are considered pluripotent instead of totipotent because they do not have the ability to become part of the extra-embryonic membranes or the placenta.

A video on how stem cells work and develop.

Although there is not complete agreement among scientists of how to identify stem cells, most tests are based on making sure that stem cells are undifferentiated and capable of self-renewal. Tests are often conducted in the laboratory to check for these properties.

One way to identify stem cells in a lab, and the standard procedure for testing bone marrow or hematopoietic stem cell (HSC), is by transplanting one cell to save an individual without HSCs. If the stem cell produces new blood and immune cells, it demonstrates its potency.

Clonogenic assays (a laboratory procedure) can also be employed in vitro to test whether single cells can differentiate and self-renew. Researchers may also inspect cells under a microscope to see if they are healthy and undifferentiated or they may examine chromosomes.

To test whether human embryonic stem cells are pluripotent, scientists allow the cells to differentiate spontaneously in cell culture, manipulate the cells so they will differentiate to form specific cell types, or inject the cells into an immunosuppressed mouse to test for the formation of a teratoma (a benign tumor containing a mixture of differentiated cells).

Scientists and researchers are interested in stem cells for several reasons. Although stem cells do not serve any one function, many have the capacity to serve any function after they are instructed to specialize. Every cell in the body, for example, is derived from first few stem cells formed in the early stages of embryological development. Therefore, stem cells extracted from embryos can be induced to become any desired cell type. This property makes stem cells powerful enough to regenerate damaged tissue under the right conditions.

Tissue regeneration is probably the most important possible application of stem cell research. Currently, organs must be donated and transplanted, but the demand for organs far exceeds supply. Stem cells could potentially be used to grow a particular type of tissue or organ if directed to differentiate in a certain way. Stem cells that lie just beneath the skin, for example, have been used to engineer new skin tissue that can be grafted on to burn victims.

A team of researchers from Massachusetts General Hospital reported in PNAS Early Edition (July 2013 issue) that they were able to create blood vessels in laboratory mice using human stem cells.

The scientists extracted vascular precursor cells derived from human-induced pluripotent stem cells from one group of adults with type 1 diabetes as well as from another group of healthy adults. They were then implanted onto the surface of the brains of the mice.

Within two weeks of implanting the stem cells, networks of blood-perfused vessels had been formed - they lasted for 280 days. These new blood vessels were as good as the adjacent natural ones.

The authors explained that using stem cells to repair or regenerate blood vessels could eventually help treat human patients with cardiovascular and vascular diseases.

Additionally, replacement cells and tissues may be used to treat brain disease such as Parkinson's and Alzheimer's by replenishing damaged tissue, bringing back the specialized brain cells that keep unneeded muscles from moving. Embryonic stem cells have recently been directed to differentiate into these types of cells, and so treatments are promising.

Healthy heart cells developed in a laboratory may one day be transplanted into patients with heart disease, repopulating the heart with healthy tissue. Similarly, people with type I diabetes may receive pancreatic cells to replace the insulin-producing cells that have been lost or destroyed by the patient's own immune system. The only current therapy is a pancreatic transplant, and it is unlikely to occur due to a small supply of pancreases available for transplant.

Adult hematopoietic stem cells found in blood and bone marrow have been used for years to treat diseases such as leukemia, sickle cell anemia, and other immunodeficiencies. These cells are capable of producing all blood cell types, such as red blood cells that carry oxygen to white blood cells that fight disease. Difficulties arise in the extraction of these cells through the use of invasive bone marrow transplants. However hematopoietic stem cells have also been found in the umbilical cord and placenta. This has led some scientists to call for an umbilical cord blood bank to make these powerful cells more easily obtainable and to decrease the chances of a body's rejecting therapy.

Another reason why stem cell research is being pursued is to develop new drugs. Scientists could measure a drug's effect on healthy, normal tissue by testing the drug on tissue grown from stem cells rather than testing the drug on human volunteers.

The debates surrounding stem cell research primarily are driven by methods concerning embryonic stem cell research. It was only in 1998 that researchers from the University of Wisconsin-Madison extracted the first human embryonic stem cells that were able to be kept alive in the laboratory. The main critique of this research is that it required the destruction of a human blastocyst. That is, a fertilized egg was not given the chance to develop into a fully-developed human.

The core of this debate - similar to debates about abortion, for example - centers on the question, "When does life begin?" Many assert that life begins at conception, when the egg is fertilized. It is often argued that the embryo deserves the same status as any other full grown human. Therefore, destroying it (removing the blastocyst to extract stem cells) is akin to murder. Others, in contrast, have identified different points in gestational development that mark the beginning of life - after the development of certain organs or after a certain time period.

People also take issue with the creation of chimeras. A chimera is an organism that has both human and animal cells or tissues. Often in stem cell research, human cells are inserted into animals (like mice or rats) and allowed to develop. This creates the opportunity for researchers to see what happens when stem cells are implanted. Many people, however, object to the creation of an organism that is "part human".

The stem cell debate has risen to the highest level of courts in several countries. Production of embryonic stem cell lines is illegal in Austria, Denmark, France, Germany, and Ireland, but permitted in Finland, Greece, the Netherlands, Sweden, and the UK. In the United States, it is not illegal to work with or create embryonic stem cell lines. However, the debate in the US is about funding, and it is in fact illegal for federal funds to be used to research stem cell lines that were created after August 2001.

Medical News Today is a leading resource for the latest headlines on stem cell research. So, check out our stem cell research news section. You can also sign up to our weekly or daily newsletters to ensure that you stay up-to-date with the latest news.

This stem cells information section was written by Peter Crosta for Medical News Today in September 2008 and was last updated on 19 July 2013. The contents may not be re-produced in any way without the permission of Medical News Today.

Disclaimer: This informational section on Medical News Today is regularly reviewed and updated, and provided for general information purposes only. The materials contained within this guide do not constitute medical or pharmaceutical advice, which should be sought from qualified medical and pharmaceutical advisers.

Please note that although you may feel free to cite and quote this article, it may not be re-produced in full without the permission of Medical News Today. For further details, please view our full terms of use

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What are Stem Cells? - Health News - Medical News Today

Skin Stem Cells Comments Off on What are Stem Cells? – Health News – Medical News Today | May 23rd, 2017

UCalgary researchers identify 'signal' crucial to stem cell function in hair follicles UCalgary News 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 ... and more »

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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

Skin Stem Cells Comments Off on Mice embryos from skin cells and by 2037 human embryos from skin cells – Next Big Future | May 23rd, 2017

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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MIAMI, May 22, 2017 /PRNewswire/ -- Longeveron announced receiving a $750,000 grant from the Maryland Stem Cell Research Fund (MSCRF) to continue groundbreaking stem cell research. Longeveron, a Miami based regenerative medicine company, will partner with the University of Maryland and Johns Hopkins University to conduct a clinical trial for Hypoplastic Left Heart Syndrome (HLHS), a rare and often fatal condition in infants caused by an underdeveloped heart.

According to Dr. Sunjay Kaushal, Director of Pediatric Cardiac Surgery at University of Maryland, and Site Investigator on this award, "We anticipate that the HLHS trial may be a game changing procedure to improve the ventricular performance for these HLHS babies that will improve their outcomes and allow them to live longer lives."

The MSCRF was established by the Governor and the Maryland General Assembly through the Maryland Stem Cell Research Act of 2006 to accelerate research using human stem cells and advance medical treatment. In a May 10 news release, Rabbi Avram Reisner, Chair of the Maryland Stem Cell Research Commission noted, "The awards announced are the first in our new Accelerating Cure initiative. They represent some of the most advanced regenerative medicine projects that are being undertaken. These awardees are at the leading edge of medical innovation and exemplify the purpose and mission of the Maryland Stem Cell Research Fund."

Longeveron Co-Founder & Chief Science Officer, Joshua M. Hare, M.D., who will serve as the Principal Investigator on this award stated, "Longeveron is honored to receive this competitive award from MSCRF to continue this important research to treat this life-threatening condition affecting infants."

About Longeveron Longeveron is a regenerative medicine therapy company founded in 2014. Longeveron's goal is to provide the first of its kind biological solution for aging-related diseases, and is dedicated to developing safe cell-based therapeutics to revolutionize the aging process and improve quality of life. The company's research focus areas include Alzheimer's disease, Aging Frailty and the Metabolic Syndrome. Longeveron produces LMSCs in its own state-of-the-art cGMP cell processing facility. http://www.longeveron.com

Contact: Suzanne Liv Page spage@longeveron.com 305.909.0850

To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/longeveron-to-receive-grant-from-the-maryland-stem-cell-research-fund-300461323.html

SOURCE Longeveron

About Longeveron

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Longeveron to receive Grant from the Maryland Stem Cell Research Fund - PR Newswire (press release)

Cardiac Stem Cells Comments Off on Longeveron to receive Grant from the Maryland Stem Cell Research Fund – PR Newswire (press release) | May 22nd, 2017

He was tired of the daily pain that made even shaking someone's hand almost unbearable.

Marlette lost his arm in an accident when he was a teenager, but as an active kid, he didn't this slow him down. He continued to play football and golf, running track and even wrestling.

But over time, the strain on his remaining arm and wrist took a toll.

So to relieve his pain, he traveled from Sioux Falls, South Dakota, to Munich, Germany, with the hopes that a special procedure using stem cells could make a difference.

"There's no cartilage," Marlette said of his wrist. "I'm bone-on-bone. It is constantly inflamed and very sore."

As Marlette grew older, even the simplest things, like tucking in his shirt or putting on a jacket, became incredibly painful.

Marlette developed cysts and holes in the bones of his wrist. Doctors prescribed anti-inflammatory medications, but they only managed the pain, doing nothing to actually heal the problem. One day, his doctor, Dr. Bob Van Demark at Sanford Health in South Dakota, where Marlette works in finance, saw a presentation by Dr. Eckhard Alt.

It was about a new treatment using stem cells.

"Following an infection or wound or trauma," Alt said, "there comes a call to the stem cells in the blood vessels, which are silent, and nature activates those cells."

Stem cells are located throughout our bodies, like a reserve army offering regeneration and repair. When we're injured or sick, our stem cells divide and create new cells to replace those that are damaged or killed. Depending on where the cells are in the body, they adapt, becoming specialized as blood cells, muscle cells or brain cells, for example.

Alt was the first person to use adipose tissue, or fat, as a prime source of stem cells, according to Dr. David Pearce, executive vice president for research at Sanford health.

"He observed that the simplest place to get some stem cells is really from the fat," said Pearce. "Most of us could give some fat up, and those stem cells don't have to be programmed in any way, but if you put in the right environment, they will naturally turn into what the cell type around them is."

Fat tissue has a lot of blood vessels, making it a prime source of stem cells, and Alt recognized that stem cells derived from adipose tissue are also particularly good at becoming cartilage and bone.

Bone marrow is another source of stem cells, but these easily turn into blood and immune cells. Stem cells from fat have another fate.

"Fat-derived stem cells have a different lineage they can turn into, that is really cartilage and bone and other sort of connective tissues," said Pearce.

Van Demark traveled to Alt's Munich clinic along with some doctors from Sanford, which is now partnering with Alt on clinical trials in the United States. Marlette's doctor was impressed with what he saw and recommended the treatment to his patient.

Marlette paid his own way to Munich, where he would receive an injection of stem cells from his own fat tissue.

"I had one treatment, and my wrist felt better almost within the next couple weeks," Marlette said. "Through the course of the next seven months, it continued to feel better and better."

One injection was enough for this ongoing improvement.

"We see (from an MRI scan) that those cysts are gone, the bone has restructured, the inflammation is gone, and he formed ... new cartilage," said Alt.

MRIs confirmed what he was feeling: The cartilage had begun to regenerate in his wrist. Because the procedure uses autologous cells, which are cells from the patient's own body, there's little to no chance of rejection by the body's immune system.

Though the procedure worked for Marlette, the use of stem cells as a form of treatment is not without controversy or risk. In the US, they have been mired in controversy because much of the early research and discussion has been centered around embryonic and fetal stem cells.

Marlette traveled to Germany because approved treatments like this are not available in the United States. Clinics have popped up across the country, but they lack oversight from the Food and Drug Administration.

Dr. Robin Smith, founder of the Stem for Life Foundation, first began working in this field 10 years ago. According to Smith, there were 400 clinical trials for stem cells when she first started; now, there are 4,500. She partnered with the Vatican to hold a stem cell conference last year.

"We're moving toward a new era in medicine," said Smith, who was not involved in this research. "(We are) recognizing cells in our body and immune system can be used in some way -- manipulated, redirected or changed at the DNA level -- to impact health and cure disease. It is an exciting time."

Dr. Nick Boulis is a neurosurgeon with Emory University in Atlanta. His team ran the first FDA-approved clinical trials in the US to inject stem cells in the spinal cords of patients with ALS, better known as Lou Gehrig's disease, and he isn't surprised to see procedures like the one at Alt's clinic in Germany have success.

"Joints and bones heal," Boulis said. "The nervous system is very bad at healing. It doesn't surprise me that we're seeing successes in recapitulating cartilage before we're seeing successes in rebuilding the motherboard."

Smith also cautioned patients to do their research, especially about the types of cells being used. "When you have a health problem, and you need a solution, sometimes you don't have three five, seven years to get there," she said, referencing the slow progression of regulations in places like the United States.

"So really ,look for places that have the regulatory approval of the country they're in. Safety has to be number one," she said.

Alt's Munich clinic was approved by the European equivalent of the FDA, the European Medicines Agency. Through the partnership with Sanford, the health group is now launching clinical trials in America, focusing on rotator cuff injuries, a common shoulder injury. This is the first FDA-approved trial of its kind.

Further down the line, Alt hopes to see stem cells used for such issues as heart procedures and treating the pancreas to help diabetics. For him, the growth is limitless.

"I think it will be exponential," he said. "It will be the same thing (we saw) with deciphering the human genome. The knowledge will go up exponentially, and the cost will go exponentially down. For me, the most exciting thing is to see how you can help patients that have been desperate for which there was no other option, no hope, and how well they do."

For Marlette, it has meant a wrist free from pain and a life free from pain medication.

Since the procedure in August, he hasn't taken any of the anti-inflammatory drugs. "I have more range of motion with my wrist, shaking hands didn't hurt anymore," he said. "My wrist seems to continue to improve, and there's less and less pain all the time."

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Patient uses fat stem cells to repair his wrist - CNN

Bone Marrow Stem Cells Comments Off on Patient uses fat stem cells to repair his wrist – CNN | May 22nd, 2017

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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Back to Browse Journals Clinical Ophthalmology Volume 11

Carina Costa Cotrim, Luiza Toscano, Andr Messias, Rodrigo Jorge, Rubens Camargo Siqueira

Department of Ophthalmology, Otorhinolaryngology and Head and Neck Surgery, Ribeirao Preto School of Medicine, University of Sao Paulo, Sao Paulo, Brazil

Purpose: To evaluate the therapeutic potential and safety of intravitreal injections of bone marrow mononuclear fraction (BMMF) containing CD34+ cells in patients with atrophic age-related macular degeneration (AMD). Methods: Ten patients with atrophic AMD and best-corrected visual acuity (BCVA) in the worse-seeing eye of 20/100 were enrolled in this study. The bone marrow from all patients was aspirated and processed for mononuclear cell separation. A 0.1mL suspension of BMMF CD34+ cells was injected into the vitreous cavity of the worse-seeing eye. Patients were evaluated at Baseline and 1,3,6,9 and 12 months after injection. Ophthalmic evaluation included BCVA measurement, microperimetry, infrared imaging, fundus autofluorescence and SD-optical coherence tomography at all study visits. Fluorescein angiography was performed at Baseline and at 6and 12 months after intravitreal therapy. Results: All patients completed the 6-month follow-up, and six completed the 12-month follow-up. Prior to the injection, mean BCVA was 1.18 logMAR (20/320-1), ranging from 20/125 to 20/640-2, and improved significantly at every follow-up visit, including the 12-month one, when BCVA was 1.0 logMAR (20/200) (P<0.05). Mean sensitivity threshold also improved significantly at 6, 9 and 12 months after treatment (P<0.05). Considering the area of atrophy identified by fundus autofluorescence, significant mean BCVA and mean sensitivity threshold improvement were observed in patients with the smallest areas of atrophy. Fluorescein angiography did not identify choroidal new vessels or tumor growth. Conclusion: The use of intravitreal BMMF injections in patients with AMD is safe and is associated with significant improvement in BCVA and macular sensitivity threshold. Patients with small areas of atrophy have a better response. The paracrine effect of CD34+ cells may explain the functional improvement observed; however, larger series of patients are necessary to confirm these preliminary findings. Keywords: AMD, stem cells, hematopoietic cells

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

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Intravitreal use of bone marrow mononuclear fraction containing CD34 + stem cells in patients with atrophic age ... - Dove Medical Press

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Science World Report

Bone Marrow Stem Cell Transplants Could Advance ALS Treatment Science World Report The researchers discovered that bone marrow stem cell transplants may advance the treatment of the disease amyotrophic lateral sclerosis (ALS). The transplants enhanced the motor functions and nervous system conditions in mice with ALS that modeled in ... Stem cell transplants beneficial to mice with ALSLife Science Daily all 2 news articles »

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Rio Sugimura

Researchers made these blood stem cells and progenitor cells from human induced pluripotent stem cells.

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 today in Nature1, 2, offers hope to people with leukaemia 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 nature1. 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 cells2.

For many years, people have figured out parts of this recipe, but theyve never quite gotten there, says Mick Bhatia, a stem-cell researcher at McMaster University in Hamilton, Canada, who was not involved with either study. This is the first time researchers have checked all the boxes and made blood stem cells.

Daleys team chose skin cells and other cells taken from adults as their starting material. Using a standard method, they reprogrammed the cells into induced pluripotent stem (iPS) cells, which are capable of producing many other cell types. Until now, however, iPS cells have not been morphed into cells that create blood.

The next step was the novel one: Daley and his colleagues inserted seven transcription factors genes that control other genes into the genomes of the iPS cells. Then they injected these modified human cells into mice to develop. Twelve weeks later, the iPS cells had transformed into progenitor cells capable of making the range of cells found in human blood, including immune cells. The progenitor cells are tantalizingly close to naturally occurring haemopoetic blood stem cells, says Daley.

Bhatia agrees. Its pretty convincing that George has figured out how to cook up human haemopoetic stem cells, he says. That is the holy grail.

By contrast, Rafiis team generated true blood stem cells from mice without the intermediate step of creating iPS cells. The researchers began by extracting cells from the lining of blood vessels in mature mice. They then inserted four transcription factors into the genomes of these cells, and kept them in Petri dishes designed to mimic the environment inside human blood vessels. There, the cells morphed into blood stem cells and multiplied.

When the researchers injected these stem cells into mice that had been treated with radiation to kill most of their blood and immune cells, the animals recovered. The stem cells regenerated the blood, including immune cells, and the mice went on to live a full life more than 1.5 years in the lab.

Because he bypassed the iPS-cell stage, Rafii compares his approach to a direct aeroplane flight, and Daleys procedure to a flight that takes a detour to the Moon before reaching its final destination. Using the most efficient method to generate stem cells matters, he adds, because every time a gene is added to a batch of cells, a large portion of the batch fails to incorporate it and must be thrown out. There is also a risk that some cells will mutate after they are modified in the lab, and could form tumours if they are implanted into people.

But Daley and other researchers are confident that the method he used can be made more efficient, and less likely to spur tumour growth and other abnormalities in modified cells. One possibility is to temporarily alter gene expression in iPS cells, rather than permanently insert genes that encode transcription factors, says Jeanne Loring, a stem-cell researcher at the Scripps Research Institute in La Jolla, California. She notes that iPS cells can be generated from skin and other tissue that is easy to access, whereas Rafiis method begins with cells that line blood vessels, which are more difficult to gather and to keep alive in the lab.

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, Bhatia says. I hoped the critics were wrong, and now I know they were.

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Lab-grown blood stem cells produced at last - Nature.com

Skin Stem Cells Comments Off on Lab-grown blood stem cells produced at last – Nature.com | May 22nd, 2017

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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By Anette Breindl Senior Science Editor

"With the advent of targeted cancer therapies, what we've found is that many of them are cardiotoxic," Saptarsi Haldar told BioWorld Today. "Pathways that are effective in cancer are toxic in the heart."

In the May 17, 2017, issue of Science Translational Medicine, Haldar, who is an associate investigator at the Gladstone Institute of Cardiovascular Disease, and his colleagues showed that a class of epigenetic drugs, the BET bromodomain inhibitors, may be not just an exception to that rule, but a class of drugs that has therapeutic utility in heart failure.

The team showed that the bromodomain inhibitor JQ-1 had therapeutic benefits in two separate animal models of advanced heart failure, but did not affect the beneficial changes to heart muscle cells that are a consequence of exercise.

The paper shows a potential new approach to heart failure an indication that, with a five-year survival rate of 60 percent, needs them.

It also shows a potential approach to another vexing problem, namely drugging transcription factors.

"There's a surprisingly tractable therapeutic index for drugging transcription in diseases," Haldar said.

While BRD4 is not itself a transcription factor, inhibiting it "dampens the transcription factor-driven network that's driving the disease . . . This is really about dampening transcriptional rewiring," he added.

In heart failure, those happen to be innate immune signaling and fibrotic signaling. Experiments in cardiac cells derived from induced pluripotent stem cells (iPSCs) showed that JQ-1 acted by blocking the activation of innate immune and profibrotic pathways, essentially preventing heart cells from rewiring themselves in maladaptive ways in response to being chronically overworked.

Haldar said the original idea to test whether the compound would have an effect in heart failure was based on "an educated guess."

Previous work had shown that certain epigenetic marks, namely acetyl marks on lysines, play a role in heart failure.

"There is a lot known about lysine acetylation in heart failure," Haldar said, and there had been previous attempts at targeting the process, which had "fallen to the wayside, in part because of issues with therapeutic index."

Even studying the molecular details of lysine acetylation's role in heart failure was challenging, because genetic approaches are not viable.

The problem became tractable with the synthesis of JQ-1 in the laboratory of James Bradner, who is a co-author on the Science Translational Medicine paper. The compound, which has been used to gain insight into epigenetic aspects of a large number of biological processes thanks to the decision of its developers to distribute it freely, targets BRD4, a "reader" protein that recognizes acetylated lysines. (See BioWorld Insight, Aug. 12, 2013.)

With the advent of JQ-1, Haldar said, "we immediately made the connection that here's a target BRD4 that you could specifically modulate that is recognizing acetyl-lysines on chromatin."

The team initially published work in 2013 showing that JQ-1 affected cellular processes in heart failure, and was an effective therapeutic in mice when given very early in the disease.

Patients, though, don't show up in their doctor's office very early in the disease. They show up with "pre-existing, often chronic heart failure," Haldar said.

At that point, the heart has already undergone significant remodeling that includes fibrosis and an activation of innate immune pathways.

The work now published in Science Translational Medicine showed that JQ-1 had effects even when given to mice that had established heart failure either due to a heart attack, or pressure overload, but did not block exercise-induced remodeling.

The team is hoping to test JQ-1 derivatives in large animal models, and ultimately take them into the clinic. Haldar is a co-founder of Tenaya Therapeutics Inc., a company launched in December with a $50 million series A financing from The Column Group. Haldar said that while he holds a patent on BET protein inhibition in heart disease, BET proteins are only "one of many targets/pathways that Tenaya is considering."

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Researchers show cancer drug class has cardiac benefits - BioWorld Online

Cardiac Stem Cells Comments Off on Researchers show cancer drug class has cardiac benefits – BioWorld Online | May 21st, 2017