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

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

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

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

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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

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

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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Cancer drug class has cardiac benefits - BioWorld Online

Cardiac Stem Cells Comments Off on Cancer drug class has cardiac benefits – BioWorld Online | May 20th, 2017

"Creative Medical Technology Holdings will develop this patent through the same process that we are using for our clinical-stage Caverstem procedure for erectile dysfunction," stated Timothy Warbington, President and Chief Executive Officer of the Company. "We plan to identify and engage key opinion leaders who will lead clinical trials, which will serve as the basis for accelerated commercialization."

The Company is currently running a clinical trial using autologous non-manipulated bone marrow stem cells for patients suffering from erectile dysfunction that are non-responsive to standard approaches such as Viagra.Once the trial is completed, the results will serve as the basis for marketing of disposables utilized in administration of stem cells.

"Although numerous companies are injecting stem cells directly into the disc, direct injection may only cause temporary benefit because the root cause of the pathology, in our opinion, is the reduced blood supply," stated Dr. Amit Patel, Director of Thoracic Surgery at University of Miami and co-founder of Creative Medical Technology Holdings. "By recreating in the microenvironment of the lower back the same thing that we do in atherosclerotic heart patients, we believe we have a novel way to treat this terrible condition that wreaks havoc on our health care system."

Several studies have shown that administration of stem cells possesses a therapeutic effect in cardiac conditions associated with poor circulation by stimulation of new blood vessel production, a process termed "angiogenesis".The current patent covers stimulation of angiogenesis in the lower back using mesenchymal stem cells.These cells can be used from the same patient, which is considered an "autologous therapy" as well as using stem cells in a universal donor manner, which is termed "allogeneic".

"The acquisition of this patent not only positions the company to expand into the disc degenerative space, but also provides a powerful platform for collaboration with other companies that are administering regenerative cells directly into the nucleus pulposus of the disc," commented Thomas Ichim, Ph.D., Chief Scientific Officer of the Company and inventor of the technology. "Stem cells are like seeds, they need to be planted into fertile soil. We feel that in certain patients it is essential to treat the lumbar ischemia, which is present in some patients suffering from disc degenerative disease, which will then allow the stem cells administered directly in the disc to perform their regenerative effects."

About US

Creative Medical Technology Holdings, Inc. is a clinical-stage biotechnology company with two focus areas; 1) personalized stem cell procedures for sexual dysfunction and infertility, and 2) universal, off-the-shelf amniotic fluid-based stem cells that possess superior healing potential without negative medical or ethical issues. Through our own research and collaborations with leading academic institutions, we have developed proprietary protocols, built an extensive intellectual property portfolio, developed complete treatment offerings for erectile dysfunction and are performing ground-breaking research with our amniotic fluid-based stem cell.

For additional information visit http://www.CREATIVEMEDICALTECHNOLOGY.com

Forward-Looking StatementsThis release may contain "forward-looking statements." Forward-looking statements are identified by certain words or phrases such as "may", "aim", "will likely result", "believe", "expect", "anticipate", "estimate", "intend", "plan", "contemplate", "seek to", "future", "objective", "goal", "project", "should", "will pursue" and similar expressions or variations of such expressions. These forward-looking statements reflect the Company's current expectations about its future plans and performance. These forward-looking statements rely on a number of assumptions and estimates which could be inaccurate and which are subject to risks and uncertainties. Actual results could vary materially from those anticipated or expressed in any forward-looking statement made by the Company. Please refer to the Company's most recent Forms 10-Q and 10-K and subsequent filings with the SEC for a further discussion of these risks and uncertainties. The Company disclaims any obligation or intent to update the forward-looking statements in order to reflect events or circumstances after the date of this release.

To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/creative-medical-technology-holdings-to-expand-into-10-billion-dollar-per-year-lower-back-pain-market-with-acquisition-of-issued-us-stem-cell-patent-300459902.html

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Creative Medical Technology Holdings to Expand into 10 Billion Dollar per Year Lower Back Pain Market with ... - PR Newswire (press release)

Cardiac Stem Cells Comments Off on Creative Medical Technology Holdings to Expand into 10 Billion Dollar per Year Lower Back Pain Market with … – PR Newswire (press release) | May 19th, 2017

May 17, 2017 Images of heart muscle cells derived from induced pluripotent stem cells. Credit: Q. Duan et al., Science Translational Medicine (2017)

A team of researchers at the Gladstone Institutes uncovered a new strategy to treat heart failure, a leading contributor to mortality and healthcare costs in the United States. Despite widespread use of currently-approved drugs, approximately 40% of patients with heart failure die within 5 years of their initial diagnosis.

"The current standard of care is clearly not sufficient, which highlights the urgent need for new therapeutic approaches," said Saptarsi Haldar, MD, an associate investigator at Gladstone and senior author of a new study featured on the cover of the scientific journal Science Translational Medicine. "In our previous work, we found that a drug-like small molecule called JQ1 can prevent the development of heart failure in mouse models when administered at the very onset of the disease. However, as the majority of patients requiring treatment already have longstanding cardiac dysfunction, we needed to determine if our strategy could also treat established heart failure."

As part of an emerging treatment strategy, drugs derived from JQ1 are currently under study in early-phase human cancer trials. These drugs act by inhibiting a protein called BRD4, a member of a family of proteins called BET bromodomains, which directly influences heart failure. With this study, the scientists found that JQ1 can effectively treat severe, pre-established heart failure in both small animal and human cell models by blocking inflammation and fibrosis (scarring of the heart tissue).

"It has long been known that inflammation and fibrosis are key conspirators in the development of heart failure, but targeting these processes with drugs has remained a significant challenge," added Haldar, who is also a practicing cardiologist and an associate professor in the Department of Medicine at the University of California, San Francisco. "By inhibiting the function of the protein BRD4, an approach that simultaneously blocks both of these processes, we are using a new and different strategy altogether to tackle the problem."

Currently available drugs used for heart failure work at the surface of heart cells. In contrast, Haldar's approach goes to the root of the problem and blocks destructive processes in the cell's command center, or nucleus.

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"We treated mouse models of heart failure with JQ1, similarly to how patients would be treated in a clinic," said Qiming Duan, MD, PhD, postdoctoral scholar in Haldar's lab and co-first author of the study. "We showed that this approach effectively treats pre-established heart failure that occurs both after a massive heart attack or in response to persistent high blood pressure (mechanical overload), suggesting it could be used to treat a wide array of patients."

Using Gladstone's unique expertise, the scientists then used induced pluripotent stem cells (iPSCs), generated from adult human skin cells, to create a type of beating heart cell known as cardiomyocytes.

"After testing the drug in mice, we wanted to check whether JQ1 would have the same effect in humans," explained co-first author Sarah McMahon, a UCSF graduate student in Haldar's lab. "We tested the drug on human cardiomyocytes, as they are cells that not only beat, but can also trigger the processes of inflammation and fibrosis, which in turn make heart failure progressively worse. Similar to our animal studies, we found that JQ1 was also effective in human heart cells, reaffirming the clinical relevance of our results."

The study also showed that, in contrast to several cancer drugs that have been documented to cause cardiac toxicity, BRD4 inhibitors may be a class of anti-cancer therapeutics that has protective effects in the human heart.

"Our study demonstrates a new therapeutic approach to successfully target inflammation and fibrosis, representing a major advance in the field," concluded Haldar. "We also believe our current work has important near-term translational impact in human heart failure. Given that drugs derived from JQ1 are already being tested in cancer clinical trials, their safety and efficacy in humans are already being defined. This key information could accelerate the development of a new heart failure drug and make it available to patients more quickly."

Explore further: Heart failure is as 'malignant' as some common cancers

More information: Q. Duan el al., "BET bromodomain inhibition suppresses innate inflammatory and profibrotic transcriptional networks in heart failure," Science Translational Medicine (2017). stm.sciencemag.org/lookup/doi/10.1126/scitranslmed.aah5084

A new analysis finds that, despite advances in care, men and women with a diagnosis of heart failure continue to have worse survival rates than patients with certain common cancers.

Patching a damaged heart with a patient's own muscle stem cells improves symptoms of heart failure, according to a Phase I clinical trial reported in Journal of the American Heart Association, the Open Access Journal of the ...

Researchers have completed a randomized clinical trial in patients with heart failure with preserved ejection fraction (HFpEF), which currently has no effective treatment for reducing morbidity and mortality.

A new analysis describes different classifications of patients who are hospitalized with acute heart failure based on various characteristics, which may help guide early decisions regarding triage and treatment.

(HealthDay)Patients with rheumatoid arthritis (RA) have increased risk of heart failure, according to a study published in the March 14 issue of the Journal of the American College of Cardiology.

In the largest German survey on heart failure to date, investigators found that the overall awareness of heart failure has not increased over the past decade and is not at a satisfactory level.

Shortness of breath is the No.1 complaint of people suffering from heart failure. Now a University of Guelph researcher has discovered its surprising cause - and an effective treatment - in a groundbreaking new study.

A team of researchers at the Gladstone Institutes uncovered a new strategy to treat heart failure, a leading contributor to mortality and healthcare costs in the United States. Despite widespread use of currently-approved ...

Although the absolute difference in U.S. county-level cardiovascular disease mortality rates have declined substantially over the past 35 years for both ischemic heart disease and cerebrovascular disease, large differences ...

Waist-to-hip ratio may be a stronger indicator of some cardiovascular illnesses than the commonly-used measure BMI, according to a new UCL-led study.

New research has found that genetic differences in antibody genes alter individuals' susceptibility to rheumatic heart disease, a forgotten inflammatory heart condition known as 'RHD' that is rife in developing countries.

People who use commonly prescribed non-steroidal anti-inflammatory drugs (NSAIDs) to treat pain and inflammation could be raising their risk of having a heart attack, as early as in the first week of use and especially within ...

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Cancer-cardiac connection illuminates promising new drug for heart ... - Medical Xpress

Cardiac Stem Cells Comments Off on Cancer-cardiac connection illuminates promising new drug for heart … – Medical Xpress | May 19th, 2017

Heavy increases in obesity have led to an epidemic of various heart diseases, including cardiac arrests and even strokes. These dangers have compelled doctors and research specialists to seek out new ways of managing these problems. One method that has been getting a lot of attention is regenerative medicine.

This treatment method, while occasionally controversial, shows an incredible potential that could solve many serious health problems. Specialists like Dr. Cameron Clokie, a health expert with decades of experience, are currently trying to find ways to make this treatment method more accepted by those who oppose it.

The Potential for Serious Health Benefits is Huge

Regenerative medicine is the use of stem cells and other regeneration items to promote more efficient healing. Dr. Cameron Clokie has preached about the effectiveness of this treatment method for years. And it seems like the rest of the world is finally catching up with him and others like him. For example, a recent study found that stem cells could help manage cardiac and nervous system diseases.

The careful use of stem cells could regenerate damaged heart tissues and help a person avoid heart attacks and other serious problems. Even more promising, stem cells could be used to help repair nerve damage that would otherwise leave a person paralyzed for life.

Stem Cell Research Could Save Lives

Think of the stem cells in your body as building blocks that will take whatever shape is necessary. They can become heart cells and patch a hole in this vital organ. However, they could also become spinal cells and repair severe damage to this crucial part of the body.

The possibilities associated with stem cells could be potentially limitless. As they can be manipulated to take the form of any cell, they could be used to treat a variety of serious health problems. For example, they could become white blood cells and fight serious viral problems. In fact, they could even be used to treat life-threatening diseases like AIDS.

One of the understated benefits of regenerative medicine is the way that it uses actual cells from your body. Think of the problems the medical world has had with artificial hearts. While they can be beneficial to many people, they are often rejected by the fickle body as an intruder. However, creating a working heart with your body's stem cells would eliminate that problem.

Why? Your body would recognize the heart's cells as coming from you and would accept it more readily. As a result, you could get a new (and real) heart to replace a severely damaged one.

Profit Levels Could Also Be High

One thing that has interested many people about regenerative health and stem cell research is the potential for huge profits. Many health experts have tried to stress the ways that regenerative health could help boost the world's economy. For example, a recent study on the financial state of this market found that it had an $18.9 billion global impact.

Even more shocking, it was projected to hit $53 billion by 2021. The major focus of this market would be in bone and joint reconstruction. The United States was expected to potentially make the largest profits in this area, which is something Dr. Cameron Clokie has emphasized in the past.

However, the European market is projected to be even bigger if the currently somewhat stagnant American regenerative market is held back by restrictive regulations or laws. In this way, well-meaning politicians could deny their constituents access to lifesaving treatments and severely impact the market at the same time.

Final Thoughts

Regenerative medicine of the type proposed by Dr. Cameron Clokie and others like him could transform the medical world. While the protests of people who find stem cells wrong are understandable, the major benefits of using them cannot be ignored.

This fact is why it is so important to help specialists like Dr. Cameron Clokie get the help they need to promote regenerative medicine breakthroughs. In this way, it is possible to solve serious health dangers.

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Canadian Doctors Like Cameron Clokie Are The Innovators Behind The New Era of Regenerative Medicine - French Tribune

Cardiac Stem Cells Comments Off on Canadian Doctors Like Cameron Clokie Are The Innovators Behind The New Era of Regenerative Medicine – French Tribune | May 19th, 2017

A team of researchers at the Gladstone Institutes uncovered a new strategy to treat heart failure, a leading contributor to mortality and healthcare costs in the United States. Despite widespread use of currently-approved drugs, approximately 40% of patients with heart failure die within 5 years of their initial diagnosis.

"The current standard of care is clearly not sufficient, which highlights the urgent need for new therapeutic approaches," said Saptarsi Haldar, MD, an associate investigator at Gladstone and senior author of a new study featured on the cover of the scientific journal Science Translational Medicine. "In our previous work, we found that a drug-like small molecule called JQ1 can prevent the development of heart failure in mouse models when administered at the very onset of the disease. However, as the majority of patients requiring treatment already have longstanding cardiac dysfunction, we needed to determine if our strategy could also treat established heart failure."

As part of an emerging treatment strategy, drugs derived from JQ1 are currently under study in early-phase human cancer trials. These drugs act by inhibiting a protein called BRD4, a member of a family of proteins called BET bromodomains, which directly influences heart failure. With this study, the scientists found that JQ1 can effectively treat severe, pre-established heart failure in both small animal and human cell models by blocking inflammation and fibrosis (scarring of the heart tissue).

"It has long been known that inflammation and fibrosis are key conspirators in the development of heart failure, but targeting these processes with drugs has remained a significant challenge," added Haldar, who is also a practicing cardiologist and an associate professor in the Department of Medicine at the University of California, San Francisco. "By inhibiting the function of the protein BRD4, an approach that simultaneously blocks both of these processes, we are using a new and different strategy altogether to tackle the problem."

Currently available drugs used for heart failure work at the surface of heart cells. In contrast, Haldar's approach goes to the root of the problem and blocks destructive processes in the cell's command center, or nucleus.

"We treated mouse models of heart failure with JQ1, similarly to how patients would be treated in a clinic," said Qiming Duan, MD, PhD, postdoctoral scholar in Haldar's lab and co-first author of the study. "We showed that this approach effectively treats pre-established heart failure that occurs both after a massive heart attack or in response to persistent high blood pressure (mechanical overload), suggesting it could be used to treat a wide array of patients."

Using Gladstone's unique expertise, the scientists then used induced pluripotent stem cells (iPSCs), generated from adult human skin cells, to create a type of beating heart cell known as cardiomyocytes.

"After testing the drug in mice, we wanted to check whether JQ1 would have the same effect in humans," explained co-first author Sarah McMahon, a UCSF graduate student in Haldar's lab. "We tested the drug on human cardiomyocytes, as they are cells that not only beat, but can also trigger the processes of inflammation and fibrosis, which in turn make heart failure progressively worse. Similar to our animal studies, we found that JQ1 was also effective in human heart cells, reaffirming the clinical relevance of our results."

The study also showed that, in contrast to several cancer drugs that have been documented to cause cardiac toxicity, BRD4 inhibitors may be a class of anti-cancer therapeutics that has protective effects in the human heart.

"Our study demonstrates a new therapeutic approach to successfully target inflammation and fibrosis, representing a major advance in the field," concluded Haldar. "We also believe our current work has important near-term translational impact in human heart failure. Given that drugs derived from JQ1 are already being tested in cancer clinical trials, their safety and efficacy in humans are already being defined. This key information could accelerate the development of a new heart failure drug and make it available to patients more quickly."

Story Source:

Materials provided by Gladstone Institutes. Note: Content may be edited for style and length.

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Cancer-cardiac connection illuminates promising new drug for heart failure - Science Daily

Cardiac Stem Cells Comments Off on Cancer-cardiac connection illuminates promising new drug for heart failure – Science Daily | May 18th, 2017

Cardiovascular disease is the number one cause of death worldwide in men, women and children, claiming more than 17 million lives each year. The effects of congestive heart failure and acute myocardial infarction (heart attack) present great challenges for doctors and researchers alike.

In this section:

Heart attacks cause damage to the heart muscle, making it less efficient at pumping blood throughout the circulatory system.

Your heart is constructed of several types of cells. For mending damaged heart tissue, researchers generally focus on three specific heart cell types:

Gladstone Institutes. Close up of a mouse heart stained to reveal the important structural protein that helps heart muscle cells to contract (red). The cell nuclei are labeled in magenta.

Despite major advances in how heart disease is managed, heart disease is progressive. Once heart cells are damaged, they cannot be replaced efficiently, at least not as we understand the heart today.

There is evidence that the heart has some repair capability, but that ability is limited and not yet well understood.

Heart failure is a general term to describe a condition in which the hearts blood-pumping action is weaker than normal. How much weaker varies widely from person to person, but the weakness typically gets worse over time. Blood circulates more slowly, pressure in the heart increases, and the heart is unable to pump enough oxygen and other nutrients to the rest of the body. To compensate, the chambers of the heart may stretch to hold more blood, or the walls of the chambers may thicken and become stiff. Eventually, the kidneys respond to the weaker blood-pumping action by retaining more water and salt, and fluid can build up in the arms, legs, ankles, feet, and even around the lungs. This general clinical picture is called congestive heart failure.

Many conditions can lead to congestive heart failure. Among the most common are:

The American Heart Association defines normal blood pressure for an adult as 120/80 or lower. What do those numbers mean? The top number is the systolic pressure that is, the pressure in your arteries when your heart beats, or contracts. The bottom number measures diastolic pressure, or the pressure in your arteries between beats, when the heart refills with blood.

In the early stages of congestive heart failure, treatment focuses on lifestyle changes (healthy diet, regular exercise, quitting smoking, etc.) and specific medications; the goals are to slow down any progression of the disease, lessen symptoms and improve quality of life.

Medications called beta blockers are often prescribed after a heart attack or to treat high blood pressure. Other medications called ACE inhibitors prevent heart failure from progressing.

For moderate to severe congestive heart failure, surgery may be necessary to repair or replace heart valves or to bypass coronary arteries with grafts. In severe cases, patients may be put on fluid and salt restriction and/or have pacemakers or defibrillators implanted to control heart rhythms.

Acute myocardial infarction, or a heart attack, occurs when the blood vessels that feed the heart are blocked, often by a blood clot that forms on top of the blockage. The blockage is a build-up of plaque that is composed of fat, cholesterol, calcium and other elements found in the blood. Without oxygen and other nutrients from the blood, heart cells die, and large swaths of heart tissue are damaged.

After a heart attack, scar tissue often forms over the damaged part of the heart muscle, and this scar tissue impairs the hearts ability to keep beating normally and pumping blood efficiently. The heart ends up working harder, which weakens the remaining healthy sections of the heart; over time, the patient experiences more heart-related health issues.

Doctors often use a procedure called angioplasty to disrupt the blood clot and widen clogged arteries. Angioplasty involves inserting and inflating a tiny balloon into the affected artery. Sometimes this temporary measure is enough to restore blood flow. However, angioplasty is often combined with the insertion of a small wire mesh tube called a stent, which helps keep the artery open and reduces the chances that it will get blocked again.

Other post-heart attack treatments include the regular use of blood thinners (for example, low-dose aspirin) to prevent new clots from forming and other medications to help control blood pressure and blood cholesterol levels. Lifestyle changes, such as lowering salt and fat intake, exercising regularly, reducing alcohol consumption and quitting smoking are also recommended to reduce the chances of a subsequent heart attack.

Scientists and clinicians have long suspected and recently confirmed that a persons genetic makeup contributes to the likelihood of their having a heart attack. Learn more here

The goals of heart disease research are to understand in greater detail what happens in heart disease and why, and to find ways to prevent damage or to repair or replace damaged heart tissue. Scientists have learned much about how the heart works and the roles different cells play in both normal function and in disease, and they are learning more about how cardiomyocytes and cardiac pacemaker cells operate, including how they communicate with each other and how they behave when damage occurs.

Researchers grow cardiomyocytes in the lab from the following sources:

These cells will beat in unison in a culture dish, the same way they do in a living heart muscle. This is exciting to consider, as researchers explore whether they might someday grow replacement tissue for transplantation into patients. However, it is not yet known whether lab-grown cardiomyocytes will integrate or beat in unison with surrounding cells if they are transplanted into the human body.

Gordon Keller Lab. Heart cells beating in a culture dish.

Scientists also use various types of stem cells to study the hearts natural repair mechanisms and test ways to enhance those repair functions. The evidence we have so far suggest thats the heart may have a limited number of cardiac stem cells that may conduct some repair and replacement functions throughout an individuals life, but we dont know where they live in the heart or how they become activated.

Human cells made from iPS cells are also incredibly useful for creating human models of heart disease to get a better understanding of exactly what goes wrong and for testing different drugs or other treatments. They can also be used to help predict which patients might have toxic cardiac side effects from drugs for other diseases such as cancer.

The key to treating heart disease is finding a way to undo the damage to the heart. Researchers are trying several tactics with stem cells to repair or replace the damaged heart tissue caused by congestive heart failure and heart attacks.

Areas under investigation include:

The Europe-wide BAMI clinical trial (the effect of intracoronary reinfusion of bone marrow-derived mononuclear cells on all-cause mortality in acute myocardial infarction) that began in 2014, is testing the infusion of cells from the participants bone marrow into one of the coronary arteries (one of two major arteries that supply the heart) to spark repair activity. However, it is not yet clear whether these cells will support heart repair function or in what way.

Researchers are also exploring transplantation of cardiomyocytes generated from both iPS cells and cardiac progenitor cells. They need to determine whether these transplanted cells survive and function in the body and whether they help speed up the hearts innate repair mechanisms.

Some of these approaches are still being evaluated in the lab while others are already being tested in clinical trials around the world. However, these trials are in their early stages and the results will not be clear for many years. Indeed, some published data conflict in critical ways, so carefully designed and well-monitored trials are key to working out what is safe and effective.

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Heart disease on Stem Cells - ISSCR

Cardiac Stem Cells Comments Off on Heart disease on Stem Cells – ISSCR | May 15th, 2017

Panaji: To ensure the number of emergency deaths due to cardiac-related problems are brought down, health minister Vishwajit Rane announced the signing of an MoU with ST Elevation Myocardial Infarction (STEMI) India. The organization, he said, has a protocol to handle cardiac emergency cases where such cases will be dealt with at the point of contact through the GVK 108 service.

Doctors will be trained to operate within the protocol he said, adding that it will help increase the window period after a cardiac attack and give treatment to a patient. "The whole idea is to save lives and if the window period is extended it will help saving lives of patients," he said, adding that significant damage happens to a patient's heart if the heart problem is not addressed.

"The problem is all casualty cases are referred to medicine and not directly to cardiology." These, he said, should immediately be looked at by the cardiac team, he said, adding that a proposal has gone to the chief minister to add three more cardiac consultants to the cardiology wing so that 24 x7 services are made available for patients.

New fleet of 108 ambulance with trained personnel including motorcycle ambulances will be pressed into service by the end of June and first week of July, he said.

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May 11, 2017

An analysis of data from the entire development program consisting of three trials assessing the feasibility of using a stem cell therapy (CD34+ cells) to treat patients with the most severe cases of angina, refractory angina (RA), showed a statistically significant improvement in exercise time as well as a reduction in mortality. Results from "CD34+ Stem Cell Therapy Improves Exercise Time and Mortality in Refractory Angina: A Patient Level Meta-Analysis" were presented today as a late-breaking clinical trial at the Society for Cardiovascular Angiography and Interventions (SCAI) 2017 Scientific Sessions in New Orleans.

One of the warning signs of coronary artery disease is angina, or chest pain, which occurs when the heart muscle does not receive enough blood. Unlike angina pectoris or "stable angina," which can often be treated with medication, RA can be incapacitating, impacting quality of life. In the most severe cases, those with class III or IV angina, treatment options are exhausted, and patients remain severely debilitated. Unfortunately, one of the untoward consequences of the improved survival of patients with chronic ischemic heart disease is more patients with refractory angina.

A meta-analysis of three trials that each showed promising results looked at injecting RA patients with autologous CD34+ cellswhich have been shown to increase blood flowand the therapy's effect on mortality and total exercise time (TET), an important predictor of long-term mortality.

Data from 304 patients was extracted and analyzed from phase 1 (24 patients), ACT-34 and ACT-34 extension studies (168 patients), and RENEW (112 patients), which was prematurely terminated by the sponsor due to financial considerations.

"The goal of this meta-analysis was to combine patient level data from three very similar trials to try understand what it would tell us," said lead investigator Tom Povsic, MD, FSCAI, associate professor at the Duke Clinical Research Institute (DCRI) and an interventional cardiologist at Duke University School of Medicine.

Results showed that patients treated with CD34+ cell therapy (n=187) improved TET by 80.5 12.1, 101.8 13.7, and 90.5 14.7 seconds at three months, six months, and 12 months compared with 28.1 15.7, 48.8 18.2, and 39.5 20.3 seconds for the placebo group (n=89), resulting in treatment effects of 52.5 (p=0.002), 52.9 (p=0.009) and 50.9 (p=0.027) seconds.

The relative risk of angina was 0.90 (p=0.40), 0.81 (p=0.14), and 0.79 (p=0.17) at three months, six months, and 12 months in CD34+ treated patients.

CD34+ treatment decreased mortality by 24 months (2.6 percent vs. 11.8 percent, p=0.003). In addition, major adverse cardiac events were less frequent (29.8 percent for CD34+ patients vs. 40.0 percent for the placebo group, p=0.08).

"Therapies for these patients are direly needed," said Povsic, "and results from our meta-analysis are very compelling. Most importantly, the number of patients in our meta-analysis approximates those who were targetedfor enrollment in RENEW, the prematurely terminated phase III study. These results suggest that had RENEW been completed, a regenerative therapy for these patients might meet criteria for approval. I still think this therapy has a lot of promise."

Timothy Henry, MD, chief of cardiology at Cedars-Sinai Medical Center in Los Angeles, agrees "CD34+ cell therapy appears to be an extremely safe and effective therapy for this growing and challenging patient population with limited options."

Explore further: Stem cell therapy shows potential for difficult-to-treat RA patient population

More information: Povsic presented "CD34+ Stem Cell Therapy Improves Exercise Time and Mortality in Refractory Angina: A Patient Level Meta-Analysis" on Thursday, May 11, 2017 11:30 a.m. CDT

A study using a stem cell therapy to treat challenging refractory angina (RA) patients demonstrated promising results, including improved exercise time, reduced angina and reduced mortality. The RENEW results were presented ...

A two-year, multi-center clinical study with 167 patients with class III-IV refractory angina randomized to low and high dose CD34+ cells or placebo has revealed that patients who received either a high or low dose of CD34a ...

The absolute cumulative probability of death at 12 months was 5 percent lower for patients who received routine invasive coronary angiography and revascularization as indicated during an unstable angina admission compared ...

An injection of stem cells into the heart could offer hope to many of the 850,000 Americans whose chest pain doesn't subside even with medicine, angioplasty or surgery, according to a study in Circulation Research: Journal ...

(HealthDay)Reduced baseline levels of circulating CD34+ stem cells predict adverse cardiovascular outcomes for patients with type 2 diabetes, according to a study published online Nov. 4 in Diabetes Care.

A non-surgical treatment that uses a patient's own bone marrow stem cells to treat chest pain or angina improved both symptoms and the length of time treated patients could be physically active, according to preliminary research ...

New research has found that genetic differences in antibody genes alter individuals' susceptibility to rheumatic heart disease, a forgotten inflammatory heart condition known as 'RHD' that is rife in developing countries.

People who use commonly prescribed non-steroidal anti-inflammatory drugs (NSAIDs) to treat pain and inflammation could be raising their risk of having a heart attack, as early as in the first week of use and especially within ...

(HealthDay)When someone goes into cardiac arrest, quick action from bystanders can have a long-lasting impact, researchers say.

Cholesterol-lowering statin drugs may have been wrongly blamed for muscle pain and weakness, said a study Wednesday that pointed the finger at a psychological phenomenon called the "nocebo" effect.

A new pilot study reports that Mexican-American stroke survivors are less likely to receive inpatient rehabilitation than non-Hispanic whites.

Less than half of individuals with peripheral artery disease, which is a narrowing of arteries to the limbs, stomach and head, are treated with appropriate medications and lifestyle counseling. These findings highlight the ...

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Summary

Orbis Research Presents Global Human Embryonic Stem Cells Market Research Report which Examine into the present trends, highlights the recent market growth, sales volume, Demand Scenarios and Opportunities emerging for business players in the near future.

Description

The Global Human Embryonic Stem Cells Market is estimated to be USD XX billion in 2017 and is expected to reach USD XX billion by 2022, registering a healthy CAGR of XX%, during 2017-2022 (forecast period).

The increase in malignant, cardiac, & neurological disorders, immediate need for effective and novel therapies, the rising human embryonic stem cell awareness and better healthcare infrastructure with government initiatives are expected to accelerate the global human embryonic stem cells market, during the forecast period.

The major companies discussed in this report are

A majority of companies are investing in the human embryonic stem cell research, globally. The high-prevalence of cardiac and malignant diseases, increasing R&D investments & research initiatives, increasing support from government & private institutions and rapid growth in medical tourism are accelerating the market growth. However, the stringent regulatory guidelines and ethical & moral concerns are restraining the market.

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The global embryonic stem cells market is segmented based on application and geography. The applications segment includes regenerative medicine, stem cell biology research, tissue engineering and toxicology testing. Based on geography, the market is segmented into North America, Europe, Asia-Pacific, the Middle East & Africa and Latin America. The Asia-Pacific human embryonic stem cells market has the potential, owing to increasing initiatives of the governments & private organizations for research in human embryonic stem cells.

Key Deliverables

Market analysis, with region-specific assessments and competition analysis on a global and regional scale.

Market definition along with the identification of key drivers and restraints.

Identification of factors instrumental in changing the market scenario, growing prospective opportunities, and identification of key companies that can influence the market.

Extensively researched competitive landscape section with profiles of major companies, along with their market share.

Identification and analysis of the macro and micro factors that affect the market on both, global and regional scale.

A comprehensive list of key market players along with the analysis of their current strategic interests and key financial information.

A wide-range of knowledge and insights about the major players in the industry and the key strategies adopted by them to sustain and grow in the studied market

Insights on the major countries/regions where the industry is growing, and identify the regions that are still untapped.

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CHARLOTTESVILLE, Va. (NEWSPLEX) -- Researchers at the University of Virginia School of Medicine were looking into kidneys and learned more about the formation of the heart.

They also identified a gene that is responsible for a deadly cardiac condition.

According to a release, scientists discovered the heart's inner lining forms from the same stem cells, known as precursor cells, that turn into blood.

That means a single type of stem cell created both the blood and part of the organ that pumps it.

A particular gene, called S1P1, is necessary for the proper formation of the heart, and without it, the tissue develops a sponginess that compromises the heart's ability to contract tightly and pump blood efficiently.

That condition is called ventricular non-compaction cardiomyopathy, which often leads to early death.

"Many patients who suffer from untreatable chronic disease, including heart and kidney disease, are in waiting lists for limited organ transplantation. Therefore, there is an urgent need to understand what happens to the cells during disease and how can they be repaired," said researchers Yan Hu, PhD. "Every organ is a complex machine built by many different cell types. Knowing the origin of each cell and which genes control their normal function are the foundations for scientists to decipher the disease process and eventually to find out how to guide the cells to self-repair or even to build up a brand new organ using amended cells from the patients."

The researchers were looking into how the kidneys form when they noted a deletion of the S1P1 gene in research mice led to deadly consequences elsewhere in the bodies of the mice.

"We were studying the role of these genes in the development of the vasculature of the kidney," said Maris Luisa S. Sequeira-Lopez, MD, of UVA's Child Health Research Center. "The heart is the first organ that develops, and so when we deleted this gene in these precursor cells, we found that it resulted in abnormalities of the heart, severe edema, hemorrhage and low heart rate."

In looking closer at the heart, the researchers discovered the gene deletion caused thin heart walls and other cardiac problems in developing mice embryos.

"For a long time, scientists believed that each organ developed independently of other organs, and the heart developed from certain stem cells and blood developed from blood stem cells," said researcher Brian C. Belyea, MD, of the UVA Children's Hospital. "A number of studies done in this lab and others, including this work, shows that there's much more plasticity in these precursor cells. What we found is that cardiac precursor cells that are present in the embryonic heart do indeed give rise to components of the heart in adults but also give rise to the blood cells."

He also said the discovery may one day lead to the development of better treatments for the cardiac condition.

The findings have been published in the journal Scientific Reports.

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Q: Ive been reading a lot about stem cells recently. Willstem cell research change the treatment of heart disease?

A: Theres some exciting early data where scientists have been able to use stem cells for regeneration of cardiac tissue, in particular certain parts of the heart or maybe even an entire heart in mice or rats.

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However, its not been done yet in humans reliably and that would be the next step. If the research bears out, we may see this as an option for heart patients in perhaps five to 10 years.

The area where stem cells might first be used is in patients who have had damage to their heart because of a heart attack. These patients have scarring on the heart and that area of the heart is not beating anymore. If we can regenerate cardiac tissue to replace this scarred tissue, the hope is to get the heart fully working again.

Growing whole new hearts will likely be later down the line and will depend on the success of the research.

Preventive cardiologistHaitham Ahmed, MD, MPH

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Will Stem Cell Research Change Treatment of Heart Disease? - Health Essentials from Cleveland Clinic (blog)

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Fixing broken hearts through tissue engineering Science Daily Menasche has placed engineered heart tissue derived from embryonic stem cell-derived cardiac cells onto the hearts of six heart attack patients in France in an initial safety study for this engineered tissue approach. Wu has used single-cell RNA ...

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Kidney research leads to surprising discovery about how the heart forms Science Daily "For a long time, scientists believed that each organ developed independently of other organs, and the heart developed from certain stem cells and blood developed from blood stem cells," explained researcher Brian C. Belyea, MD, of the UVA Children's ... and more »

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MedicalResearch.com (blog)

Three Distinct Cardiac Stem Cell Populations Isolated from a Single Human Heart Biopsy MedicalResearch.com (blog) Response: In the field of cardiovascular research there is ongoing debate regarding the optimal cell population(s) to use for the treatment of patients with heart failure. A major reason being, the lack of understanding of the actions and synergism ...

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Newswise BIRMINGHAM, Ala. The third annual Cardiovascular Tissue Engineering Symposium met at the University of Alabama at Birmingham last month, a gathering of noted physicians and scientists who share the goal of creating new tissues and new knowledge that can prevent or repair heart disease and heart attacks.

Talks ranged from the cutting-edge translational work of Phillippe Menasche, M.D., Ph.D., professor of thoracic and cardiovascular surgery, Paris Descartes University, to the basic biology research of Sean Wu, M.D., Ph.D., an associate professor of medicine, Stanford University School of Medicine. Menasches work pioneers human treatment with engineered heart tissue. Wus work opens the door to generating heart chamber-specific cardiomyocytes from human induced pluripotent stem cells, which act similarly to embryonic stem cells, having the potential to differentiate into any type of cell.

Menasche has placed engineered heart tissue derived from embryonic stem cell-derived cardiac cells onto the hearts of six heart attack patients in France in an initial safety study for this engineered tissue approach. Wu has used single-cell RNA sequencing to show 18 categories of cardiomyocytes in the heart, differing by cell type and anatomical location, even though they all derived from the same lineage.

We are creating a new community of engineer-scientists, said Jay Zhang, M.D., Ph.D., chair and professor of the UAB Department of Biomedical Engineering. In their welcoming remarks, both Selwyn Vickers, M.D., dean of the UAB School of Medicine, and Victor Dzau, M.D., professor of medicine at Duke University School of Medicine and president of the National Academy of Medicine, spoke of the growing convergence between scientists and physicians that is leading to tremendous possibilities to improve patient care.

The tissue engineering field is moving fast.

Cardiac progenitor cells that can contribute to growth or repair injury in the heart were only discovered in 2003, says symposium presenter Michael Davis, Ph.D., associate professor of Medicine, Department of Biomedical Engineering, Georgia Tech College of Engineering and Emory University School of Medicine. In 2006, the Japanese scientist Shinya Yamanaka first showed how to transform adult cells into induced pluripotent stem cells. This potentially provides feedstock for tissue engineering using either pluripotent cells or specific progenitor cells for certain tissue lineages.

One example of the pace of change was given by Bjorn Knollman, M.D., Ph.D., professor of medicine and pharmacology at Vanderbilt University School of Medicine. Knollman noted an ugly truth that everyone recognized in 2013 that cardiomyocytes derived from induced pluripotent stem cells were nothing like normal adult cardiomyocytes in shape, size and function.

He described the improved steps like culturing the derived cardiomyocytes in a Matrigel mattress and giving them a 14-day hormone treatment that have led to derived cardiomyocytes with greatly improved cell volume, morphology and function. His take-home message: In just four years, from 2013 to 2017, researchers were able to remove the differences between induced pluripotent stem cell-derived cardiomyocytes and normal adult cardiomyocytes.

In other highlights of the symposium, Joo Soares, Ph.D., a research scientist for the Center for Cardiovascular Simulation, University of Texas at Austin, explained how subjecting engineered heart valve tissue to cyclic flexure as it is grown in a bioreactor leads to improved quantity, quality and distribution of collagen, as opposed to tissue that is not mechanically stressed.

Sumanth Prabhu, M.D., professor and chair of the Division of Cardiovascular Disease, UAB School of Medicine, talked about the role of immune cells in cardiac remodeling and heart failure. He noted the distinct phases after a heart attack acute inflammation and dead tissue degradation, zero to four days; the healing phase of resolution and repair, four to 14 days; and the chronic ischemic heart failure that can occur weeks to months later. Prabhu described experiments to show how specialized spleen macrophages specifically marginal-zone metallophilic macrophages migrate to the heart after a heart attack and are required for heart repair to commence.

Nenad Bursac, Ph.D., professor of Biomedical Engineering, Duke University School of Medicine, described his advances in engineering vascularized heart tissue for repair after a heart attack. Bursac said a better understanding of how to grow the tissue from heart tissue progenitor cells has allowed formation of mature giga patches up to 4 centimeters square that have good propagation of heartbeat contractions and spontaneous formation of capillaries from derived-vascular endothelial and smooth muscle cells. These patches are being tested in pigs.

Duke Universitys Victor Dzau gave a perspective of the paracrine hypothesis over the past 15 years. In 2003, researchers had seen that applying mesenchymal stem cells to a heart attack area led to improved heart function, with beneficial effects seen as early as 72 hours. However, there was little engraftment and survival of the stem cells. Thus was born the hypothesis, which has been worked out in detail since then that stem cells do their work by release of biologically active factors that act on other cells, similar to the way that paracrine hormones have their effect only in the vicinity of the gland secreting it.

Joseph Wu, M.D., Ph.D., professor of radiology, Stanford University School of Medicine, showed how heart cells derived from induced pluripotent stem cells could be used to develop personalized medicine approaches for cancer patients. The problem, he explained, is that some cancer patients are susceptible to a deadly cardiotoxicity when treated with the potent drug doxorubicin. Hence, the drug has a black box warning, the strictest warning mandated by the Food and Drug Administration. Wu was able to use a library of induced pluripotent stem cell-derived cardiomyocytes to associate certain genotypes and phenotypes with doxorubicin sensitivity, in what he called a clinical trial in a dish. From this knowledge, it will be possible to look at the transcriptome profile in patient-specific cardiomyocytes derived from induced pluripotent stem cells to predict patient-specific drug safety and efficacy, thus fulfilling the definition of precision medicine the right treatment at the right time to the right person.

In all, UABs Cardiovascular Tissue Engineering Symposium included more than 30 presentations. The entire symposium will be summarized in a paper for the journal Circulation Research, expected to be published shortly, Zhang says.

Presentations of the 2015 Cardiovascular Tissue Engineering Symposium were published in the journal Science Translational Medicine, and the presentations of the 2016 Cardiovascular Tissue Engineering Symposium were published in the journal Circulation Research.

At UAB, Zhang holds the T. Michael and Gillian Goodrich Endowed Chair of Engineering Leadership, Vickers holds the James C. Lee Jr. Endowed Chair for the Dean of the School of Medicine, and Prabhu holds the Mary Gertrude Waters Chair of Cardiovascular Medicine.

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