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Archive for the ‘Cardiac Stem Cells’ Category

How oxygen-producing pond scum could save your life after a heart attack – Los Angeles Times

If youre having a heart attack, your life might someday be saved by pond scum.

Thats because these lowly bacteria are capable of producing something a stricken heart desperately needs: oxygen.

In fact, when Stanford scientists injected massive doses of cyanobacteria into the hearts of rats who suffered the equivalent of a widow-maker heart attack, oxygen levels ballooned by a factor of 25.

The results, published Wednesday in the journal Science Advances, suggest a truly original approach to reducing the damage done to heart muscle when it is suddenly deprived of oxygen.

When blood flow to the heart is interrupted by a clot or the narrowing of vessels, the effect can be deadly, either now or later. Its not uncommon for a heart attack victim to survive his or her immediate ordeal, only to succumb to heart failure the effects of heart muscle weakened by its brush with oxygen deprivation months or years after the event.

Physicians have long sought to avert that lingering damage by restoring the flow of oxygenated blood to the heart muscle as quickly as possible. Wielding an arsenal of drugs, stents, grasping devices, saws, scalpels and long, threaded catheters, cardiac surgeons try to isolate, remove or dissolve clots in the arteries feeding the heart before cells start to die off and lasting damage is done. More recently, stem cells have shown great promise in restoring damaged heart muscle.

But this new approach to rescuing living tissue from so-called ischemic damage proceeds from the observation that oxygen abounds in our atmosphere as a result of photosynthesis the fuel-making industry of green plants all around us.

If a lack of oxygen is the problem when living tissue is deprived of blood flow, perhaps we should invite into our bodies the forests genius for manufacturing the gas our cells depend on to survive.

Every day we walk around and see trees, said Dr. Joseph Woo, chair of Stanford School of Medicines department of cardiothoracic surgery and the papers senior author. We wondered, would there be any possibility of taking plants and putting them next to the heart and getting them to work together?

Several years ago, researchers in Woos Stanford lab started by grinding spinach, and then kale, with mortar and pestle. When they introduced the green slurry to living tissue in Petri dishes and set them in the sun, nothing happened.

But when they tried a more primitive practitioner of photosynthesis pond scum the oxygenation effect was clear to see.

The scientists used cyanobacteria, the blue-green algae that often blooms on the surface of still waters, to supply life-giving oxygen to the stricken hearts of rats. After clamping off the largest of three arteries feeding blood to the heart the left anterior descending coronary artery the researchers injected those hearts with tens of millions of the single-celled organisms.

For two full hours one hour while the clamp remained in place and a second hour after it was removed the animals incisions remained open. During that time, the hearts of the treated rats were exposed to strong light, which jump-started the photosynthetic process.

Just as they would on the surface of a pond, the cyanobacteria used the pigment chlorophyll to combine water, carbon dioxide and light to produce glucose. The incidental byproduct of that process oxygen kept cells deprived of oxygenated blood from dying off in droves.

A day later, the damage to the hearts of treated rats was less than half as severe as that seen in rats that got an inactive treatment, according to the study.

And four weeks after the ischemic crisis, the hearts of rats that got the photosynthesis treatment performed dramatically better than the hearts of rats that did not.

In humans, an improvement in heart function of the magnitude shown in treated rats would have profound clinical implications, the Stanford team wrote. If humans were to reap benefits as great as those seen in the lab rats, they added, such a treatment probably would spell the difference between a healthy patient and one suffering from heart failure.

Woo sees the new research as a proof of principle that photosynthesis, in some form, might someday be used as a bridge treatment for patients who have had blood flow cut off to any organ. It might be useful in sustaining organs harvested for transplant during their long journey to a new owner, Woo said, and in preventing the death of brain cells during a stroke. It may even one day improve the treatment of malignant tumors that thrive in oxygen-deprived environments, he added.

But in its current form, a photosynthetic bridge treatment is far from ready for use in clinical settings.

It would be very suboptimal to have to crack someones chest open and shine the light on them to begin the oxygenation process, Woo said. To work around that impracticality, a team at Stanford is already working on supercharged versions of the cyanobacteria that rescued rats hearts in his teams new paper.

Researchers may have to engineer ways other than direct exposure to visible light to jump-start the photosynthesis process, he said. Plants or cyanobacteria may be amenable to genetic engineering that would allow them to produce oxygen more copiously, or to initiate photosynthesis in response to energy at wavelengths that can penetrate skin and other tissue.

Remarkably, the direct injection into the heart of millions of cyanobacteria did not cause any infection. Nor did it prompt the rats immune systems to mount a defensive response a reaction that can be just as deadly as infection.

Virtually all of the millions of single-celled organisms injected into the rats hearts were gone 24 hours after the experiment. And in a more thorough search four weeks later, the researchers could find no sign of infection or of lingering bacterial cells anywhere near the hearts of rats who got the treatment.

If cyanobacteria were someday to play a key role in the treatment of human disease, it would be a nice footnote to an already striking record of accomplishment. Thats because cyanobacteria one of the largest, oldest and most important groups of bacteria on Earth are already pretty much responsible for life as we know it.

In the Archaean and Proterozoic eons 2.5 billion years ago, cyanobacteria flourished by using light and carbon dioxide for nourishment. The oxygen given off by this photosynthesis created Earths oxygen-rich atmosphere, making the evolution of ever more complex life forms possible.

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How oxygen-producing pond scum could save your life after a heart attack – Los Angeles Times

Domainex, Imperial College London Extend Cardiac Therapy Collaboration – Genetic Engineering & Biotechnology News

Domainex will expand its two-year-old collaboration with Imperial College London to discover new therapies that reduce heart muscle damage during heart attacks, the partners said today.

Domainex and Imperial aim to discover a treatment that inhibits the enzyme MAP4K4, which is linked to cell death following heart attacks. Since the collaboration was launched in 2015, the partners said, they have discovered novel, potent, and selective MAP4K4 inhibitors using human cardiac muscle grown from human induced pluripotent stem cells (iPSCs).

The inhibitors have shown promise in protecting these cells against oxidative stress, a trigger for cell death during heart attacks, Domainex and Imperial said.

As a result of the progress, Imperial College London said, its Professor Michael Schneider, Ph.D., has secured a follow-on award of 4.5 million (nearly $5.8 million) from the Wellcome Trusts Seeding Drug Discovery initiative to continue the research.

From its Medicines Research Centre near Cambridge, U.K., Domainex said, its researchers will continue to provide integrated drug discovery servicesincluding further biochemical, cellular and biophysical assay screening, and structure-guided medicinal chemistry coupled with drug metabolism, safety, and pharmacokinetic assessment of promising candidates.

Domainex and Imperial said they aim to advance potential treatments into preclinical development and ultimately to clinical evaluation.

“We have already identified a number of very exciting, novel inhibitors through structure-based drug design,” Domainex CSO Trevor Perrior said in a statement. The innovative cardiac muscle assay developed by the team here at Domainex working in partnership with Imperial College London, is enabling early testing on human cardiac muscle cells, which will make cardiac drug discovery more efficient and effective in identifying efficacious candidate drugs.

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Domainex, Imperial College London Extend Cardiac Therapy Collaboration – Genetic Engineering & Biotechnology News

Domainex and Imperial step up cardiac research – Business Weekly

Drug discovery sleuths at Domainex in Cambridge have expanded a partnership with Imperial College London to find novel therapies that reduce heart muscle damage during heart attacks.

The aim is to discover a drug that inhibits the enzyme MAP4K4, which plays a key role in triggering cell death following cardiac arrest.

Significant progress made in the first two years of the collaboration has enabled Imperials Professor Michael Schneider to secure a follow-on award of 4.5 million from Wellcomes Seeding Drug Discovery scheme, to continue the pioneering research.

Since initiating the project in 2015, Domainex and Imperial College London have worked closely together to advance promising therapeutic candidates. Novel, potent, and selective MAP4K4 inhibitors have already been discovered. Using human cardiac muscle grown from human induced pluripotent stem cells, these inhibitors have shown efficacy in protecting these cells against oxidative stress, a known trigger for cell death during heart attacks.

Trevor Perrior (pictured), chief scientific officer at Domainex, said: We have already identified a number of very exciting, novel inhibitors through structure-based drug design.

We look forward to continuing our strong partnership with Professor Schneider and his team and to building on the excellent progress made to date. The innovative cardiac muscle assay developed by the team here at Domainex working in partnership with Imperial College London is enabling early testing on human cardiac muscle cells, which will make cardiac drug discovery more efficient and effective in identifying efficacious candidate drugs.

The Domainex team will continue to provide integrated drug discovery services from its Medicines Research Centre at Chesterford Research Park near Cambridge UK including further biochemical, cellular and biophysical assay screening, structure-guided medicinal chemistry, coupled with drug metabolism, safety and pharmacokinetic assessment of promising candidates. The goal is to advance the project efficiently into pre-clinical development and ultimately to clinical evaluation.

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Domainex and Imperial step up cardiac research – Business Weekly

Human Heart Tissue Grown from Stem Cells Improves Drug Testing … – Technology Networks

Researchers at the Institute of Bioengineering and Nanotechnology (IBN) of A*STAR have engineered a three-dimensional heart tissue from human stem cells to test the safety and efficacy of new drugs on the heart.

Cardiotoxicity, which can lead to heart failure and even death, is a major cause of drug withdrawal from the market. Antibiotics, anticancer and antidiabetic medications can have unanticipated side effects for the heart. So it is important to test as early as possible whether a newly developed drug is safe for human use. However, cardiotoxicity is difficult to predict in the early stages of drug development, said Professor Jackie Y. Ying, Executive Director at IBN.

A big part of the problem is the use of animals or animal-derived cells in preclinical cardiotoxicity studies due to the limited availability of human heart muscle cells. Substantial genetic and cardiac differences exist between animals and humans. There have been a large number of cases whereby the tests failed to detect cardiovascular toxicity when moving from animal studies to human clinical trials*.

Existing screening methods based on 2D cardiac structure cannot accurately predict drug toxicity, while the currently available 3D structures for screening are difficult to fabricate in the quantities needed for commercial application.

To solve this problem, the IBN research team fabricated their 3D heart tissue from cellular self-assembly of heart muscle cells grown from human induced pluripotent stem cells. They also developed a fluorescence labelling technology to monitor changes in beating rate using a real-time video recording system. The new heart tissue exhibited more cardiac-specific genes, stronger contraction and higher beating rate compared to cells in a 2D structure.

Using the 3D heart tissue, we were able to correctly predict cardiotoxic effects based on changes in the beating rate, even when these were not detected by conventional tests. The method is simple and suitable for large-scale assessment of drug side effects. It could also be used to design personalized therapy using a patients own cells, said lead researcher Dr Andrew Wan, who is Team Leader and Principal Research Scientist at IBN.

The researchers have filed a patent on their human heart tissue model, and hope to work with clinicians and pharmaceutical companies to bring this technology to market.

This article has been republished frommaterialsprovided by A*STAR. Note: material may have been edited for length and content. For further information, please contact the cited source.

Reference:

Lu, H. F., Leong, M. F., Lim, T. C., Chua, Y. P., Lim, J. K., Du, C., & Wan, A. C. (2017). Engineering a functional three-dimensional human cardiac tissue model for drug toxicity screening. Biofabrication, 9(2), 025011. doi:10.1088/1758-5090/aa6c3a

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Human Heart Tissue Grown from Stem Cells Improves Drug Testing … – Technology Networks

Heart Disease – Closer Look at Stem Cells

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 – Closer Look at Stem Cells

Stem cells regenerate external layer of a human heart – Today’s Medical Developments

Activating stem cells Wnt signaling pathways can drive cardiac progenitor cells to become epicardium instead of myocardium cells.

A process using human stem cells can generate epicardium cells that cover the external surface of a human heart, according to a multidisciplinary team of researchers.

In 2012, we discovered that if we treated human stem cells with chemicals that sequentially activate and inhibit the Wnt signaling pathway, they become myocardium muscle cells, says Xiaojun Lance Lian, assistant professor of biomedical engineering and biology, who is leading the study at Pennsylvania State University (Penn State). Myocardium, the middle of the hearts three layers, is the thick, muscular part that contracts to drive blood through the body. The Wnt signaling pathway is a group of signal transduction pathways made of proteins that pass signals into a cell using cell-surface receptors.

We needed to provide the cardiac progenitor cells with additional information in order for them to generate into epicardium cells, but prior to this study, we didnt know what that information was, Lian says. Now, we know that if we activate the cells Wnt signaling pathway again, we can re-drive these cardiac progenitor cells to become epicardium cells, instead of myocardium cells.

Lance Lian/Penn State

The groups results bring researchers one step closer to regenerating an entire heart wall. Through morphological assessment and functional assay, the researchers found that the generated epicardium cells were similar to epicardium cells in living humans and those grown in the laboratory.

The last piece is turning cardiac progenitor cells to endocardium cells (the hearts inner layer), and we are making progress on that, Lian says.

The groups method of generating epicardium cells could be useful in clinical applications, for patients who suffer a heart attack.

Heart attacks occur due to blockage of blood vessels, Lian says. This blockage stops nutrients and oxygen from reaching the heart muscle, and muscle cells die. These muscle cells cannot regenerate themselves, so there is permanent damage, which can cause additional problems. These epicardium cells could be transplanted to the patient and potentially repair the damaged region.

In addition to generating the epicardium cells, researchers can keep them proliferating in the lab after treating them with a cell-signaling pathway Transforming Growth Factor Beta (TGF) inhibitor.

After 50 days, our cells did not show any signs of decreased proliferation. However, the proliferation of the control cells without the TGF Beta inhibitor started to plateau after the tenth day, Lian says.

Pennsylvania State University http://www.psu.edu

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Stem cells regenerate external layer of a human heart – Today’s Medical Developments

Human heart tissue grown from stem cells improves drug testing – Medical Xpress

June 8, 2017 This image shows human heart muscle cells growing in the 3D tissue structure. The cells have been stained with fluorescent molecules to identify the nuclei in blue, and cardiac-specific protein, in green. Credit: Agency for Science, Technology and Research (A*STAR), Singapore

Researchers at the Institute of Bioengineering and Nanotechnology (IBN) of A*STAR have engineered a three-dimensional heart tissue from human stem cells to test the safety and efficacy of new drugs on the heart.

“Cardiotoxicity, which can lead to heart failure and even death, is a major cause of drug withdrawal from the market. Antibiotics, anticancer and antidiabetic medications can have unanticipated side effects for the heart. So it is important to test as early as possible whether a newly developed drug is safe for human use. However, cardiotoxicity is difficult to predict in the early stages of drug development,” said Professor Jackie Y. Ying, Executive Director at IBN.

A big part of the problem is the use of animals or animal-derived cells in preclinical cardiotoxicity studies due to the limited availability of human heart muscle cells. Substantial genetic and cardiac differences exist between animals and humans. There have been a large number of cases whereby the tests failed to detect cardiovascular toxicity when moving from animal studies to human clinical trials.

Existing screening methods based on 2-D cardiac structure cannot accurately predict drug toxicity, while the currently available 3-D structures for screening are difficult to fabricate in the quantities needed for commercial application.

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To solve this problem, the IBN research team fabricated their 3-D heart tissue from cellular self-assembly of heart muscle cells grown from human induced pluripotent stem cells. They also developed a fluorescence labelling technology to monitor changes in beating rate using a real-time video recording system. The new heart tissue exhibited more cardiac-specific genes, stronger contraction and higher beating rate compared to cells in a 2-D structure.

“Using the 3-D heart tissue, we were able to correctly predict cardiotoxic effects based on changes in the beating rate, even when these were not detected by conventional tests. The method is simple and suitable for large-scale assessment of drug side effects. It could also be used to design personalized therapy using a patient’s own cells,” said lead researcher Dr Andrew Wan, who is Team Leader and Principal Research Scientist at IBN.

The researchers have filed a patent on their human heart tissue model, and hope to work with clinicians and pharmaceutical companies to bring this technology to market.

This finding was reported recently in the Biofabrication journal.

Explore further: Stem cell-based screening methods may predict heart-related side effects of drugs

More information: Hong Fang Lu et al. Engineering a functional three-dimensional human cardiac tissue model for drug toxicity screening, Biofabrication (2017). DOI: 10.1088/1758-5090/aa6c3a

Coaxing stem cells from patients to become heart cells may help clinicians personalize drug treatments and prevent heart-related toxicity.

Scientists at The University of Queensland have taken a significant step forward in cardiac disease research by creating a functional ‘beating’ human heart muscle from stem cells.

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A team of biomedical engineering researchers, led by the University of Minnesota, has created a revolutionary 3D-bioprinted patch that can help heal scarred heart tissue after a heart attack. The discovery is a major step …

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Human heart tissue grown from stem cells improves drug testing – Medical Xpress

SpaceX launches CU-built heart, bone health experiments to space station – CU Boulder Today

Editors note: The SpaceX Falcon 9 rocket scheduled to launch today from Florida was delayed due to weather conditions. The launch occured on Saturday, June 3.

A SpaceX rocket wasslated to launch two University of Colorado Boulder-built payloads to the International Space Station (ISS) from Florida on Thursday, including oneto look at changes in cardiovascular stem cells in microgravity that may someday help combat heart disease on Earth.

The Dragon spacecraft

The second payload will be used for rodent studies testing a novel treatment for bone loss in space, which has been documented in both astronauts and mice. The two payloads were developed by BioServe Space Technologies, a research center within the Ann and H.J Smead Department of Aerospace Engineering,

We have a solid relationship with SpaceX and NASA that allows us to regularly fly our flight hardware to the International Space Station, said BioServe Director Louis Stodieck. The low gravity of space provides a unique environment for biomedical experiments that cannot be reproduced on Earth, and our faculty, staff and students are very experienced in designing and building custom payloads for our academic, commercial and government partners.

The experiments will be launched on a SpaceX Falcon 9 rocket from Cape Canaveral, Florida, and carried to the ISS on the companys Dragon spacecraft. The SpaceX-CRS-11 mission launching Thursday marks BioServes 55th mission to space.

The cardiovascular cell experiments, designed by Associate Professor Mary Kearns-Jonker of the Loma Linda University School of Medicine in Loma Linda, California, will investigate how low gravity affects stem cells, including physical and molecular changes. While spaceflight is known to affect cardiac cell structure and function, the biological basis for such impacts is not clearly understood, said BioServe Associate director Stefanie Countryman.

As part of the study, the researchers will be comparing changes in heart muscle stem cells in space with similar cells simultaneously cultured on Earth, said Countryman. Researchers are hopeful the findings could help lead to stem cell therapies to repair damaged cardiac tissue. The findings also could confirm suspicions by scientists that microgravity speeds up the aging process, Countryman said.

For the heart cell experiments, BioServe is providing high-tech, cell-culture hardware known as BioCells that will be loaded into shoebox-sized habitats on ISS. The experiments will be housed in BioServes Space Automated Bioproduct Lab (SABL), a newly updated smart incubator that will reduce the time astronauts spend manipulating the experiments.

The second experiment, created by Dr. Chia Soo of the UCLA School of Medicine, will test a new drug designed to not only block loss of bone but also to rebuild it.

The mice will ride in a NASA habitat designed for spaceflight to the ISS. Once on board, some mice will undergo injections with the new drug while others will be given a placebo. At the end of the experiments half of the mice will be returned to Earth in SpaceXs Dragon spacecraft and transported to UCLA for further study, said Stodieck, a scientific co-investigator on the experiment.

BioServes Space Automated Byproduct Lab

In addition to the two science experiments, BioServe is launching its third SABL unit to the ISS. Two SABL units are currently onboard ISS supporting multiple research experiments, including three previous stem cell experiments conducted by BioServe in collaboration with Stanford University, the Mayo Clinic and the University of Minnesota.

The addition of the third SABL unit will expand BioServes capabilities in an era of high-volume science on board the ISS, said Countryman.

BioServe researchers and students have flown hardware and experiments on missions aboard NASA space shuttles, the ISS and on Russian and Japanese government cargo rockets. BioServe previously has flown payloads on commercial cargo rockets developed by both SpaceX, headquartered in Hawthorne, California, and Orbital ATK, Inc. headquartered in Dulles, Virginia.

Since it was founded by NASA in 1987, BioServe has partnered with more than 100 companies and performed dozens of NASA-sponsored investigations. Itspartners include large and small pharmaceutical and biotechnology companies, universities and NASA-funded researchers, and investigations sponsored by the Center for the Advancement of Science in Space, which manages the ISS U.S. National Laboratory. CU-Boulder students are involved in all aspects of BioServe research efforts, said Stodieck.

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SpaceX launches CU-built heart, bone health experiments to space station – CU Boulder Today

3D-Printed Patch Mends Hearts – Photonics.com

Photonics.com Jun 2017 MINNEAPOLIS, June 6, 2017 A new 3D-laser-printed patch has been developed that can help heal scarred heart tissue after a heart attack.

Researchers from the University of Minnesota-Twin Cities, University of Wisconsin-Madison, and University of Alabama-Birmingham used laser-based 3D bioprinting techniques to incorporate stem cells derived from adult human heart cells on a matrix that began to grow and beat synchronously in a dish in the lab.

“This is a significant step forward in treating the No. 1 cause of death in the U.S.,” said Brenda Ogle, an associate professor of biomedical engineering at the University of Minnesota. “We feel that we could scale this up to repair hearts of larger animals and possibly even humans within the next several years.”

The patch is modeled after a digital 3D scan of the structural proteins of native heart tissue. It is then made into a physical structure by 3D printing with proteins native to the heart and further integrating cardiac cell types derived from stem cells.

“We were quite surprised by how well it worked, given the complexity of the heart,” Ogle said. “We were encouraged to see that the cells had aligned in the scaffold and showed a continuous wave of electrical signal that moved across the patch.”

The researchers will soon begin working on a larger patch and testing it on a pig heart, which is similar to a human heart.

The research study is published in the American Heart Association journal Circulation Research (doi: 10.1161/CIRCRESAHA.116.310277).

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3D-Printed Patch Mends Hearts – Photonics.com

[ June 3, 2017 ] SpaceX rocket again set for station delivery after scientists swap mice, fruit flies Mission Reports – Spaceflight Now

The Falcon 9 rocket is raised at launch pad 39A early Saturday for a second launch attempt. Credit: Spaceflight Now

A Falcon 9 rocket is again standing upright on launch pad 39A at NASAs Kennedy Space Center in Florida after ground teams lowered the booster Friday to swap out mice heading to the International Space Station for medical experiments.

Liftoff is set for 5:07 p.m. EDT (2107 GMT) to begin a nearly two-day journey to the space station, where the Dragon supply ship fixed to the top of the Falcon 9 rocket will arrive Monday.

The Dragon capsule, the first cargo craft SpaceX has refurbished and reused after a previous flight, is carrying nearly 6,000 pounds of experiments and equipment, including 40 mice inside specially-designed transporters for an investigation into a treatment that could combat bone loss in astronauts on long-duration space missions and osteoporosis in patients on the ground.

Once the mice arrive at the space station, astronauts will treat the rodents with NELL-1, a therapeutic treatment designed to promote bone growth, according to Chia Soo, the chief scientist for the experiment and a professor of plastic, reconstructive and orthopaedic surgery at UCLA.

Men and women past the age of 50, on the average, lose about a half-percent of bone mass per year, Soo said. But in microgravity conditions, the astronaut, on average, loses anywhere from 1 to 2 percent of bone mass per month.

She added that bone loss in astronauts has tremendous implications for humans with respect to long-term space travel or space habitation in microgravity because we end up progressively losing bone mass.

Twenty of the mice will return to Earth alive with the SpaceX Dragon supply ship in early July, the first time the commercial spacecraft has landed with live animals on-board. The 20 mice that come back alive will go to UCLAs laboratories for additional research and treatment.

The other 20 mice will remain on the space station for more observation and comparative studies with the mice on Earth. All of the animals will eventually be euthanized.

If successful, this will have tremendous implications for patients on Earth because if you look at statistics approximately one in every two to three females over the age of 50, or one in every four to five males over the age of 50, will have an osteoporosis-related fracture, Soo said.

We are hoping this study will give us some insights on how NELL-1 can work under these extreme conditions and if it can work for treating microgravity-related bone loss, which is a very accelerated, severe form of bone loss, then perhaps it can (be used) for patients one day on Earth who have bone loss due to trauma or due to aging or disease, Soo said.

After the Falcon 9 launch attempts scrub Thursday, teams lowered the launcher at pad 39A and installed a temporary white room on the Dragon capsules hatch to change out the rodent habitats and several other experiments.

The logistics are complicated, as you might imagine,Louis Stodieck, director of BioServe Space Technologies at the University of Colorado Boulder, wrote in an email to Spaceflight Now. We would normally be okay for two back-to-back launch attempts, but because orbital mechanics would not permit a launch attempt (Friday), the first scrub was automatically done for 48 hours rather than 24.

This forced us to reload with new animals and new Transporters (spaceflight habitats for the ride to space for the mice), Stodieck wrote. We plan for additional groups of mice just for such contingencies.

NASA spokesperson Dan Huot said other experiments that required a changeout for the two-day launch delay included a swarm of fruit flies launching to the space station to examine how prolonged spaceflight affects their heart function.

The hearts of the insects beat at about same rate as the human heart, making it a useful analog, scientists said.

We were back in the lab the night of the scrub setting up new egg collections and adult fly vials, said Karen Ocorr, a co-investigator on the fruit fly experiment from theSanford Burnham Research Institute. These replaced the original set of vials and have now been loaded onto the Dragon for todays attempt.

Researchers are sending between 4,000 and 6,000 fruit fly eggs to the space station, where they will hatch before coming back to Earth aboard the Dragon spacecraft.

We would like to understand the role of microgravity on astronaut heart function in order to try to prevent long-term effects when they are in space for long periods and after they come back, Ocorr said.

But there are real-world implications as well for people who are spending long periods of time in bedrest or immobilized, Ocorr said. We expect that what we find in our studies on the ISS will have implications for maintaining cardiac function in those sorts of situations.

Huot said two crystal growth expeiments and a payload to study how microgravity affects cardiac stem cells also needed to be replaced with the two-day launch delay.

Email the author.

Follow Stephen Clark on Twitter: @StephenClark1.

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[ June 3, 2017 ] SpaceX rocket again set for station delivery after scientists swap mice, fruit flies Mission Reports – Spaceflight Now

Vistagen Therapeutics, Inc. – Seeking Alpha

Vistagen Therapeutics, Inc.

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“VistaGen Therapeutics, Inc. (NASDAQ: VTGN), is a clinical-stage biopharmaceutical company focused on developing new generation medicines for depression and other central nervous system (CNS) disorders. Our lead CNS product candidate, AV-101, is a new generation oral antidepressant drug candidate in Phase 2 development. AV-101’s mechanism of action is fundamentally differentiated from all FDA-approved antidepressants and atypical antipsychotics used adjunctively to treat major depressive disorder (MDD), with potential to drive a paradigm shift towards a new generation of safer and faster-acting antidepressants. AV-101 is currently being evaluated by the U.S. National Institute of Mental Health (NIMH) in a Phase 2 monotherapy study in MDD being fully funded by the NIMH and conducted by Dr. Carlos Zarate Jr., Chief, Section on the Neurobiology and Treatment of Mood Disorders and Chief of Experimental Therapeutics and Pathophysiology Branch at the NIMH, and one of the world’s foremost experts on the use of low dose IV ketamine and other NMDA receptor antagonists to treat MDD. VistaGen is also preparing to launch a 180-patient Phase 2 study of AV-101 as an adjunctive treatment for MDD patients with inadequate response to standard, FDA-approved antidepressant therapies. Dr. Maurizio Fava of Harvard University will be the Principal Investigator of the Phase 2 adjunctive treatment study. AV-101 may also have the potential to treat multiple CNS disorders and neurodegenerative diseases in addition to MDD, including chronic neuropathic pain, epilepsy, Parkinson’s disease and Huntington’s disease, where modulation of the NMDAR, AMPA pathway and/or key active metabolites of AV-101 may achieve therapeutic benefit. In addition to our AV-101 programs, VistaStem, VistaGens wholly owned subsidiary, is applying our human pluripotent stem cell (hPSC) technology platform and CardioSafe 3D, our customized in-vitro human cardiac cell bioassay system, to predict potential heart toxicity of new chemical entities (NCEs) long before they are tested in preclinical animal studies and human clinical studies. Having successfully assessed AV-101 and numerous other drug candidates to establish the clinically predictive capabilities of CardioSafe 3D, we are now using CardioSafe 3D to expand our pipeline through cardiac liability-focused small molecule drug rescue, and to participate, together with a select group of companies, in the FDA’s Comprehensive in-vitro Proarrhythmia Assay (CIPA) initiative designed to change the landscape of preclinical drug development by providing a more complete and accurate assessment of potential drug effects on cardiac risk. We are also focused on collaborating with others to advance development and commercialization of medicine and cell therapy applications of our stem cell technology across a range of cell types, including blood, bone, cartilage, heart and liver cells. In December 2016, we entered into an exclusive sublicense agreement with BlueRock Therapeutics L.P, a next generation regenerative medicine company established by Bayer AG and Versant Ventures, for our rights to proprietary technologies relating to the production of cardiac stem cells for the treatment of heart disease.”

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Vistagen Therapeutics, Inc. – Seeking Alpha

SpaceX to launch CU-built heart, bone health experiments to space station – CU Boulder Today

Editors note: The SpaceX Falcon 9 rocket scheduled to launch today from Florida was delayed due to weather conditions. The launch has been rescheduled for Saturday, June 3.

A SpaceX rocket wasslated to launch two University of Colorado Boulder-built payloads to the International Space Station (ISS) from Florida on Thursday, including oneto look at changes in cardiovascular stem cells in microgravity that may someday help combat heart disease on Earth.

The Dragon spacecraft

The second payload will be used for rodent studies testing a novel treatment for bone loss in space, which has been documented in both astronauts and mice. The two payloads were developed by BioServe Space Technologies, a research center within the Ann and H.J Smead Department of Aerospace Engineering,

We have a solid relationship with SpaceX and NASA that allows us to regularly fly our flight hardware to the International Space Station, said BioServe Director Louis Stodieck. The low gravity of space provides a unique environment for biomedical experiments that cannot be reproduced on Earth, and our faculty, staff and students are very experienced in designing and building custom payloads for our academic, commercial and government partners.

The experiments will be launched on a SpaceX Falcon 9 rocket from Cape Canaveral, Florida, and carried to the ISS on the companys Dragon spacecraft. The SpaceX-CRS-11 mission launching Thursday marks BioServes 55th mission to space.

The cardiovascular cell experiments, designed by Associate Professor Mary Kearns-Jonker of the Loma Linda University School of Medicine in Loma Linda, California, will investigate how low gravity affects stem cells, including physical and molecular changes. While spaceflight is known to affect cardiac cell structure and function, the biological basis for such impacts is not clearly understood, said BioServe Associate director Stefanie Countryman.

As part of the study, the researchers will be comparing changes in heart muscle stem cells in space with similar cells simultaneously cultured on Earth, said Countryman. Researchers are hopeful the findings could help lead to stem cell therapies to repair damaged cardiac tissue. The findings also could confirm suspicions by scientists that microgravity speeds up the aging process, Countryman said.

For the heart cell experiments, BioServe is providing high-tech, cell-culture hardware known as BioCells that will be loaded into shoebox-sized habitats on ISS. The experiments will be housed in BioServes Space Automated Bioproduct Lab (SABL), a newly updated smart incubator that will reduce the time astronauts spend manipulating the experiments.

The second experiment, created by Dr. Chia Soo of the UCLA School of Medicine, will test a new drug designed to not only block loss of bone but also to rebuild it.

The mice will ride in a NASA habitat designed for spaceflight to the ISS. Once on board, some mice will undergo injections with the new drug while others will be given a placebo. At the end of the experiments half of the mice will be returned to Earth in SpaceXs Dragon spacecraft and transported to UCLA for further study, said Stodieck, a scientific co-investigator on the experiment.

BioServes Space Automated Byproduct Lab

In addition to the two science experiments, BioServe is launching its third SABL unit to the ISS. Two SABL units are currently onboard ISS supporting multiple research experiments, including three previous stem cell experiments conducted by BioServe in collaboration with Stanford University, the Mayo Clinic and the University of Minnesota.

The addition of the third SABL unit will expand BioServes capabilities in an era of high-volume science on board the ISS, said Countryman.

BioServe researchers and students have flown hardware and experiments on missions aboard NASA space shuttles, the ISS and on Russian and Japanese government cargo rockets. BioServe previously has flown payloads on commercial cargo rockets developed by both SpaceX, headquartered in Hawthorne, California, and Orbital ATK, Inc. headquartered in Dulles, Virginia.

Since it was founded by NASA in 1987, BioServe has partnered with more than 100 companies and performed dozens of NASA-sponsored investigations. Itspartners include large and small pharmaceutical and biotechnology companies, universities and NASA-funded researchers, and investigations sponsored by the Center for the Advancement of Science in Space, which manages the ISS U.S. National Laboratory. CU-Boulder students are involved in all aspects of BioServe research efforts, said Stodieck.

Continue reading here:
SpaceX to launch CU-built heart, bone health experiments to space station – CU Boulder Today

SpaceX to launch heart, bone health experiments to space station – CU Boulder Today

Editors note: The SpaceX Falcon 9 rocket scheduled to launch today from Florida was delayed due to weather conditions. The launch has been rescheduled for Saturday, June 3.

A SpaceX rocket wasslated to launch two University of Colorado Boulder-built payloads to the International Space Station (ISS) from Florida on Thursday, including oneto look at changes in cardiovascular stem cells in microgravity that may someday help combat heart disease on Earth.

The Dragon spacecraft

The second payload will be used for rodent studies testing a novel treatment for bone loss in space, which has been documented in both astronauts and mice. The two payloads were developed by BioServe Space Technologies, a research center within the Ann and H.J Smead Department of Aerospace Engineering,

We have a solid relationship with SpaceX and NASA that allows us to regularly fly our flight hardware to the International Space Station, said BioServe Director Louis Stodieck. The low gravity of space provides a unique environment for biomedical experiments that cannot be reproduced on Earth, and our faculty, staff and students are very experienced in designing and building custom payloads for our academic, commercial and government partners.

The experiments will be launched on a SpaceX Falcon 9 rocket from Cape Canaveral, Florida, and carried to the ISS on the companys Dragon spacecraft. The SpaceX-CRS-11 mission launching Thursday marks BioServes 55th mission to space.

The cardiovascular cell experiments, designed by Associate Professor Mary Kearns-Jonker of the Loma Linda University School of Medicine in Loma Linda, California, will investigate how low gravity affects stem cells, including physical and molecular changes. While spaceflight is known to affect cardiac cell structure and function, the biological basis for such impacts is not clearly understood, said BioServe Associate director Stefanie Countryman.

As part of the study, the researchers will be comparing changes in heart muscle stem cells in space with similar cells simultaneously cultured on Earth, said Countryman. Researchers are hopeful the findings could help lead to stem cell therapies to repair damaged cardiac tissue. The findings also could confirm suspicions by scientists that microgravity speeds up the aging process, Countryman said.

For the heart cell experiments, BioServe is providing high-tech, cell-culture hardware known as BioCells that will be loaded into shoebox-sized habitats on ISS. The experiments will be housed in BioServes Space Automated Bioproduct Lab (SABL), a newly updated smart incubator that will reduce the time astronauts spend manipulating the experiments.

The second experiment, created by Dr. Chia Soo of the UCLA School of Medicine, will test a new drug designed to not only block loss of bone but also to rebuild it.

The mice will ride in a NASA habitat designed for spaceflight to the ISS. Once on board, some mice will undergo injections with the new drug while others will be given a placebo. At the end of the experiments half of the mice will be returned to Earth in SpaceXs Dragon spacecraft and transported to UCLA for further study, said Stodieck, a scientific co-investigator on the experiment.

BioServes Space Automated Byproduct Lab

In addition to the two science experiments, BioServe is launching its third SABL unit to the ISS. Two SABL units are currently onboard ISS supporting multiple research experiments, including three previous stem cell experiments conducted by BioServe in collaboration with Stanford University, the Mayo Clinic and the University of Minnesota.

The addition of the third SABL unit will expand BioServes capabilities in an era of high-volume science on board the ISS, said Countryman.

BioServe researchers and students have flown hardware and experiments on missions aboard NASA space shuttles, the ISS and on Russian and Japanese government cargo rockets. BioServe previously has flown payloads on commercial cargo rockets developed by both SpaceX, headquartered in Hawthorne, California, and Orbital ATK, Inc. headquartered in Dulles, Virginia.

Since it was founded by NASA in 1987, BioServe has partnered with more than 100 companies and performed dozens of NASA-sponsored investigations. Itspartners include large and small pharmaceutical and biotechnology companies, universities and NASA-funded researchers, and investigations sponsored by the Center for the Advancement of Science in Space, which manages the ISS U.S. National Laboratory. CU-Boulder students are involved in all aspects of BioServe research efforts, said Stodieck.

Excerpt from:
SpaceX to launch heart, bone health experiments to space station – CU Boulder Today

Station Ramps Up for Cardiac Research Loaded on Dragon – Space Fellowship

The Expedition 51 crew members are awaiting a new space shipment and getting ready for new science experiments. The crew is also preparing for the departure of a pair of International Space Station flight engineers.

The Falcon 9 rocket that will launch the SpaceX Dragon cargo craft to space is resting at its launch pad today at the Kennedy Space Center in Florida. Dragon will lift off Thursday at 5:55 p.m. EDT on a three-day trip to the stations Harmony module.

Inside the commercial space freighter is nearly 6,000 pounds of crew supplies, station hardware and science experiments. One of those experiments, Cardiac Stem Cells, will research how stem cells affect cardiac biology and tissue regeneration in space. The stations Microgravity Science Glovebox is being readied for the study which may provide insight into accelerated aging due to living in microgravity.

On Friday, cosmonaut Oleg Novitskiy will command the Soyuz MS-03 spacecraft to return him and European Space Agency astronaut Thomas Pesquet back to Earth after 196 days in space. The two crew members are packing their spacecraft with research samples, hardware and personal items for the near 3.5 hour ride home. The duo will undock from the Rassvet module at 6:47 a.m. EDT. They will then parachute to a landing in Kazakhstan at 10:10 a.m. (8:10 p.m. Kazakh time).

See the article here:
Station Ramps Up for Cardiac Research Loaded on Dragon – Space Fellowship

Can Tiny Plumbing Fix Broken Hearts? – NC State News

Illustration of the heart patch using artificial capillaries.

Editors note: This is a guest post by Frances Ligler, Lampe Distinguished Professor in the Joint Department of Biomedical Engineering (BME) at NC State and UNC-Chapel Hill. This is one of a series of posts from NC State researchers that address the value of science, technology, engineering and mathematics.

Judging from evidence provided by Star Wars and The Six Million Dollar Man, repairing body parts seems to require a screwdriver. However, teams of scientists and engineers are exploring other ways to repair our bodies and NC State faculty and students are collaborating across colleges to perform cutting-edge experiments to further regenerative medicine therapeutics.

Before joining NC State, Michael Daniele (an assistant professor of BME and electrical and computer engineering) and I invented a method of making long strings of artificial blood capillaries by creating soft walls in between fluids streaming through a small channel. Cells present in the streams were incorporated into the capillaries to mimic the 3-D architecture of your capillaries and veins.

At NC State, we joined forces with Ke Cheng, an expert in stem cells and cardiology from the College of Veterinary Medicine, to incorporate these artificial capillaries into a degradable patch containing cardiac stem cells. Postdoctoral fellow Teng Su placed the patches on damaged areas of rat hearts and showed both repair of the rat heart tissue and return of the pumping capacity of the heart (which does not happen under the untreated condition where scar tissue forms in the damaged heart).

In another exciting collaboration, Matt Fisher from BME, Rohan Shirwaiker (an associate professor of industrial and systems engineering) and Behnam Pourdeyhimi from the College of Textiles are teaming up to reconstruct damaged knees. They are recreating the underlying fibrous scaffolds that support the cartilage in a manner that better mimics the original knee and supports the growth of the normal cell type within the new scaffolds which should improve healing and support a return to normal function in the knee.

The variety of skills required for this project include designing an entirely new device for printing fibers, understanding how to arrange the fibers and change their composition to accommodate bone or cartilage-forming cells, and learning how the new tissue develops to accommodate physical motion.

The lure of replacement body parts is widespread. There are far more people waiting for replacement organs than can be accommodated by human donors. Learning to use an individuals own cells to trigger tissue regeneration has far more long-term potential to address the ever-growing needs of accident victims and an aging population.

The key to success lies with teams of dedicated scientists, engineers, medical professionals and financial supporters that are focused on using the lessons learned across many fields to solve this grand challenge.

Original post:
Can Tiny Plumbing Fix Broken Hearts? – NC State News

SpaceX to launch heart, bone health experiments to space station Thursday – CU Boulder Today

A SpaceX rocket is slated to launch two University of Colorado Boulder-built payloads to the International Space Station (ISS) from Florida Thursday, including oneto look at changes in cardiovascular stem cells in microgravity that may someday help combat heart disease on Earth.

The Dragon spacecraft

The second payload will be used for rodent studies testing a novel treatment for bone loss in space, which has been documented in both astronauts and mice. The two payloads were developed by BioServe Space Technologies, a research center within the Ann and H.J Smead Department of Aerospace Engineering,

We have a solid relationship with SpaceX and NASA that allows us to regularly fly our flight hardware to the International Space Station, said BioServe Director Louis Stodieck. The low gravity of space provides a unique environment for biomedical experiments that cannot be reproduced on Earth, and our faculty, staff and students are very experienced in designing and building custom payloads for our academic, commercial and government partners.

The experiments will be launched on a SpaceX Falcon 9 rocket from Cape Canaveral, Florida and carried to the ISS on the companys Dragon spacecraft. The SpaceX-CRS-11 mission launching Thursday marks BioServes 55th mission to space.

The cardiovascular cell experiments, designed by Associate Professor Mary Kearns-Jonker of the Loma Linda University School of Medicine in Loma Linda, California, will investigate how low gravity affects stem cells, including physical and molecular changes. While spaceflight is known to affect cardiac cell structure and function, the biological basis for such impacts is not clearly understood, said BioServe Associate director Stefanie Countryman.

As part of the study, the researchers will be comparing changes in heart muscle stem cells in space with similar cells simultaneously cultured on Earth, said Countryman. Researchers are hopeful the findings could help lead to stem cell therapies to repair damaged cardiac tissue. The findings also could confirm suspicions by scientists that microgravity speeds up the aging process, Countryman said.

For the heart cell experiments, BioServe is providing high-tech, cell-culture hardware known as BioCells that will be loaded into shoebox-sized habitats on ISS. The experiments will be housed in BioServes Space Automated Bioproduct Lab (SABL), a newly updated smart incubator that will reduce the time astronauts spend manipulating the experiments.

The second experiment, created by Dr. Chia Soo of the UCLA School of Medicine, will test a new drug designed to not only block loss of bone but also to rebuild it.

The mice will ride in a NASA habitat designed for spaceflight to the ISS. Once on board, some mice will undergo injections with the new drug while others will be given a placebo. At the end of the experiments half of the mice will be returned to Earth in SpaceXs Dragon spacecraft and transported to UCLA for further study, said Stodieck, a scientific co-investigator on the experiment.

BioServes Space Automated Byproduct Lab

In addition to the two science experiments, BioServe is launching its third SABL unit to the ISS. Two SABL units are currently onboard ISS supporting multiple research experiments, including three previous stem cell experiments conducted by BioServe in collaboration with Stanford University, the Mayo Clinic and the University of Minnesota.

The addition of the third SABL unit will expand BioServes capabilities in an era of high-volume science on board the ISS, said Countryman.

BioServe researchers and students have flown hardware and experiments on missions aboard NASA space shuttles, the ISS and on Russian and Japanese government cargo rockets. BioServe previously has flown payloads on commercial cargo rockets developed by both SpaceX, headquartered in Hawthorne, California, and Orbital ATK, Inc. headquartered in Dulles, Virginia.

Since it was founded by NASA in 1987, BioServe has partnered with more than 100 companies and performed dozens of NASA-sponsored investigations. Itspartners include large and small pharmaceutical and biotechnology companies, universities and NASA-funded researchers, and investigations sponsored by the Center for the Advancement of Science in Space, which manages the ISS U.S. National Laboratory. CU-Boulder students are involved in all aspects of BioServe research efforts, said Stodieck.

Original post:
SpaceX to launch heart, bone health experiments to space station Thursday – CU Boulder Today

SpaceX rocket will be carrying CU experiments – 9NEWS.com

One of the experiments involves cardiovascular stem cells, investigating how gravity affects stem cells.

Jaime Berg, KUSA 4:47 PM. MDT May 31, 2017

Source: University of Colorado

KUSA – A SpaceX rocket is scheduled to launch Thursday — and on board will be two payloads built by researchers at the University of Colorado in Boulder. The payloads include studies that could be life-changing for people on earth.

One of the experiments involves cardiovascular stem cells. The work is with some researchers in California.

Theyre investigating how gravity affects stem cells, including physical and molecular changes. The information, could help lead to stem cell therapies to repair damaged cardiac tissue.

One of the experiments has to do with rodents.

Mice are actually being sent to the international space station, in a NASA habitat, designed for spaceflight.

The mice will be going through a series of experiments to study bone loss in space.

The experiments will be sent in shoebox sized habitats.

Both undergrad and graduate students at CU are involved in the research efforts.

2017 KUSA-TV

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SpaceX rocket will be carrying CU experiments – 9NEWS.com

Curbside Heart Risk; Ear Lobes and Stroke; Heart Pump Recall – MedPage Today

Air pollution, especially from diesel, has again been linked to heart risk, which left researchers suggesting people stay as far from the curb as possible when walking on the sidewalk. (Evening Standard)

Is a diagonal ear lobe crease a signal of stroke risk, or just a surrogate for age? (Daily Mail)

Mechanical thrombectomy for acute ischemic stroke from intracranial occlusion works at least as well for patients with extracranial carotid disease “and it should not be withheld in these complex patients with acute ischemic stroke,” MR CLEAN researchers concluded in the Annals of Internal Medicine.

A faster, cheaper protocol for noninvasive cardiac MRI with contrast tested for use in developing nations appeared feasible and impacted clinical management in 33% of patients, a study reported at EuroCMR in Prague. (EurekAlert press release)

Men may actually suffer more cardiomyopathy from chemotherapy than do women, according to other news from EuroCMR. (Cardiovascular Business)

The HeartMate II heart pump has another controller problem, with a recall following 70 incidents of malfunction when patients attempted to change out the controller on their own, including 26 deaths. Thoratec is shipping new controllers with updated software and hardware, but Mass Device reports that the key thing is for physicians to bring patients into the clinic for controller exchanges.

One lot of ticagrelor (Brilinta) physician samples bottles is being recalled after finding one with an additional medication inside (lesinurad, Zurampic) that could harm the kidneys when taken alone. (FDA MedWatch)

A new orodispersible formulation of ticagrelor (Brilinta, Brilique in Europe) was cleared by European regulators for patients who are intubated or have trouble swallowing conventional tablets. (European Pharmaceutical Review)

A novel robotic arm brace that translates tiny amounts of muscle activity into movement can help patients perform daily activities independently after a stroke, researchers report in the Archives of Physical Medicine and Rehabilitation.

The FDA posted notice of recall of a health supplement (Al-Er-G Capsules from MusclMasster) found to contain the banned substance ephedra, which poses risk of heart attack, stroke, and death.

Normalization of testosterone levels with testosterone replacement therapy was associated with less atrial fibrillation, according to a VA database study in the Journal of the American Heart Association.

A helical transendocardial infusion catheter for cardiac stem cell delivery appeared better for cell retention in a pig model. (International Heart Journal)

Adding chronic kidney disease, measures of systolic blood pressure variability, lupus, and a few other factors to the already extensive list of factors in the QRISK2 algorithm yielded good calibration for 10-year cardiovascular disease risk assessment, but performed about the same as the prior iteration. (BMJ)

Another 15 genes associated with risk for coronary artery disease were described in Nature Genetics.

2017-05-30T12:30:00-0400

See more here:
Curbside Heart Risk; Ear Lobes and Stroke; Heart Pump Recall – MedPage Today

2 Gene Variants Linked to Most Common Congenital Heart Defect – Technology Networks

Researchers are working to determine why the aortic valve doesnt form correctly in patients with the most common congenital heart defect: bicuspid aortic valve.

In a new Nature Communications study, the Michigan Medicine-led group found two genetic variants associated with the condition.

Bicuspid aortic valve is moderately heritable, yet experts are still figuring out which part of our DNA code explains why some BAV patients inherit the disease.

Weve completed the first successful genomewide study of bicuspid aortic valve, by studying subjects at U-Ms Frankel Cardiovascular Center, says first author Bo Yang, M.D., Ph.D., a Michigan Medicine cardiac surgeon. We are using state-of-the-art technology of induced stem cell and gene editing to dissect the genomic region we found to be associated with BAV. Its a great collaboration that will accelerate our scientific understanding of this disease.

BAV patients have aortic valves with only two leaflets, rather than three, limiting the valves function as the heart pumps oxygen-rich blood toward the aorta to enrich the body. The condition is associated with various complications, including a narrowed valve (aortic stenosis), a leaky valve (aortic insufficiency or regurgitation), an infection of the valve or an aortic aneurysm.

“This finding gives us a great head start toward understanding the mechanism of how a genetic change outside the protein-coding part of the genome can lead to disease.”Cristen Willer, Ph.D.

A great head start

The researchers performed genomewide association scans of 466 BAV cases from the Frankel Cardiovascular Center and 4,660 controls from the Michigan Genomics Initiative, with replication on 1,326 cases and 8,103 controls from collaborators at other leading institutions. They also reprogrammed the matured white blood cells to change them back into immortal cells (stem cells) and changed the genetic code of those cells to study the function of the variants they identified through the genomewide association study.

The team reports two genetic variants, both affecting a key cardiac transcription factor called GATA4, reached or nearly reached genomewide significance in BAV. GATA4 is a protein important to cardiovascular development in the womb, and GATA4 mutations have been associated with other cardiovascular defects.

One of the regions we identify actually changes the protein coded by the gene, and the other likely changes expression levels of GATA4 during valve formation, says senior author Cristen Willer, Ph.D., professor of internal medicine, human genetics and computational medicine and bioinformatics. Because most genetic variants associated with human disease are in the 99 percent of the genome that doesnt code for proteins, this finding gives us a great head start toward understanding the mechanism of how a genetic change outside the protein-coding part of the genome can lead to disease.

Specifically, the authors point to a disruption during the endothelial-mesenchymal transition, which is a critical step in the development of the aortic valve. Willer and Yang say this study, with support from the Frankel CVC and the Bob and Ann Aikens Aortic Program, adds new knowledge about the mechanism of BAV formation. They plan to continue to study the biological effect of both variants associated BAV in cells and animal models.

Reference

Yang, B., Zhou, W., Jiao, J., Nielsen, J. B., Mathis, M. R., Heydarpour, M., … & Fritsche, L. (2017). Protein-altering and regulatory genetic variants near GATA4 implicated in bicuspid aortic valve. Nature Communications, 8, 15481.

Read the original:
2 Gene Variants Linked to Most Common Congenital Heart Defect – Technology Networks

Over 40 U.S. National Laboratory Sponsored Experiments on SpaceX CRS-11 Destined for the International Space … – GlobeNewswire (press release)

May 26, 2017 14:28 ET | Source: Center for the Advancement of Science in Space

Kennedy Space Center, FL, May 26, 2017 (GLOBE NEWSWIRE) — The SpaceX Falcon 9 vehicle is slated to launch its 11thcargo resupply mission (CRS-11) to the International Space Station (ISS) no earlier than June 1, 2017 from Kennedy Space Center Launch Complex 39A. Onboard the Falcon 9 launch vehicle is the SpaceX Dragon spacecraft, which will carry more than 40 ISS U.S. National Laboratory sponsored experiments. This mission will showcase the breadth of research possible through the ISS National Laboratory, as experiments range from the life and physical sciences, Earth observation and remote sensing, and a variety of student-led investigations. Below highlights the investigations as part of the SpaceX CRS-11 mission:

ADVANCED COLLOIDS EXPERIMENT-TEMPERATURE CONTROLLED-6 (ACE-T-6)

Matthew Lynch, Procter & Gamble (West Chester, OH)

Implementation Partner: NASA Glenn Research Center and Zin Technologies, Inc.

Colloids are suspensions of microscopic particles in a liquid, and they are found in products ranging from milk to fabric softener. Consumer products often use colloidal gels to distribute specialized ingredients, for instance droplets that soften fabrics, but the gels must serve two opposite purposes: they have to disperse the active ingredient so it can work, yet maintain an even distribution so the product does not spoil. Advanced Colloids Experiment-Temperature-6 (ACE-T-6) studies the microscopic behavior of colloids in gels and creams, providing new insight into fundamental interactions that can improve product shelf life.

EFFICIENCY OF VERMICOMPOSTING IN A CLOSED SYSTEM (NANORACKS-NDC-BMS-VERICOMPOSTING)

Bell Middle School (Golden, CO)

Implementation Partner: NanoRacks

Vermicomposting, or using worms to break down food scraps, is an effective way to reduce waste and obtain a nutrient-rich fertilizer for plants. The NanoRacks-NDC-Bell Middle School-Efficiency of Vermicomposting in a Closed System (NanoRacks-NDC-BMS-Vermicomposting) investigation is a student-designed project that studies whether red wiggler worms, a species of earthworm, are able to produce compost in space. Results are used to study the potential for composting as a form of recycling on future long-duration space missions.

FUNCTIONAL EFFECTS OF SPACEFLIGHT ON CARDIOVASCULAR STEM CELLS (CARDIAC STEM CELLS)

Dr. Mary Kearns-Jonker, Loma Linda University (Loma Linda, CA)

Implementation Partner: BioServe Space Technologies

Functional Effects of Spaceflight on Cardiovascular Stem Cells (Cardiac Stem Cells) investigates how microgravity alters stem cells and the factors that govern stem cell activity, including physical and molecular changes. Spaceflight is known to affect cardiac function and structure, but the biological basis for this is not clearly understood. This investigation helps clarify the role of stem cells in cardiac biology and tissue regeneration. In addition, this research could confirm the hypothesis that microgravity accelerates the aging process.

MULTIPLE USER SYSTEM FOR EARTH SENSING (MUSES)

Paul Galloway, Teledyne Brown Engineering (Huntsville, AL)

Implementation Partner: Teledyne Brown Engineering

Teledyne Brown Engineering developed the Multiple User System for Earth Sensing (MUSES), an Earth imaging platform, as part of the companys new commercial space-based digital imaging business. MUSES hosts earth-viewing instruments (Hosted Payloads), such as high resolution digital cameras, hyperspectral imagers, and provides precision pointing and other accommodations. It hosts up to four instruments at the same time, and offers the ability to

change, upgrade, and robotically service those instruments. It also provides a test bed for technology demonstration and technology maturation by providing long-term access to the space environment on the ISS.

NANORACKS-JAMSS-2LAGRANGE-1

Tomohiro Ichikawa, Lagrange Corp. (Tokyo, Japan)

Implementation Partner: NanoRacks

Spaceflight affects organisms in a wide range of ways, from a reduction in human bone density to changes in plant root growth. NanoRacks-JAMSS-2 Lagrange-1 helps students understand potential spaceflight-related changes by exposing plant seeds to microgravity, and then germinating and growing them on Earth. The plants are compared with specimens grown from seeds that remained on the ground. The investigation also connects students to the space program by sending their photographic likenesses and personal messages into orbit. This connection inspires the next generation of scientists and engineers who will work on international space programs.

NEUTRON CRYSTALLOGRAPHIC STUDIES OF HUMAN ACETYLCHOLINESTERASE FOR THE DESIGN OF ACCERERATED REACTIVATORS (ORNL-PCG)

Dr. Andrey Kovalevsky, Oak Ridge National Laboratory (Oak Ridge, TN)

Implementation Partner: CASIS

The investigative team is trying to improve our understanding of acetylcholinesterase, an enzyme essential for normal communication between nerve cells and between nerve and muscle cells. As a target of deadly neurotoxins produced by animals as venom or by man as nerve agents and pesticides, understanding the structure of acetylcholinesterase is critical to designing better antidotes to poisoning by chemicals that attack the nervous system. The Oak Ridge National Lab team plans to use the microgravity environment of space to grow large crystals of the enzyme that will be imaged back on Earth using a powerful imaging approach called neutron diffraction. Neutron diffraction yields very detailed structural information but requires much larger crystals than traditional x-ray diffraction imaging methods. The investigators hypothesize that structural images of space-grown crystals will bring us closer to more effective and less toxic antidotes for neurotoxins that bind and inhibit acetylcholinesterase.

STUDENT SPACEFLIGHTS EXPERIMENT PROGRAM MISSION 10

Dr. Jeff Goldstein, National Center for Earth and Space Science Education (Washington, D.C.)

Implementation Partner: NanoRacks

The Student Spaceflight Experiments Program (SSEP) provides one of the most exciting educational opportunities available: student-designed experiments to be flown on the International Space Station. The NanoRacks-National Center for Earth and Space Science Education-Odyssey (NanoRacks-NCESSE-Odyssey) investigation contains 24 student experiments, including microgravity studies of plant, algae and bacterial growth; polymers; development of multi-cellular organisms; chemical and physical processes; antibiotic efficacy; and allergic reactions. The program immerses students and teachers in real science, providing first-hand experience conducting scientific experiments and connecting them to the space program.

SYSTEMIC THERAPY OF NELL-1 FOR OSTEOPOROSIS (RODENT RESEARCH-5)

Dr. Chia Soo, University of California at Los Angeles (Los Angeles, CA)

Implementation Partner: NASA Ames Research Center and BioServe Space Technologies

Astronauts living in space for extended durations experience bone density loss, or osteoporosis. Currently, countermeasures include daily exercise designed to prevent bone loss from rapid bone density loss deterioration. However, in space and on Earth, therapies for osteoporosis cannot restore bone that is already lost. The Systemic Therapy of NELL-1 for Osteoporosis (Rodent Research-5) investigation tests a new drug on rodents that can both rebuild bone and block further bone loss, improving health for crew members in orbit and people on Earth. Dr. Soos laboratory has been funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases within the National Institutes of Health. This experiment builds on those previous research investigations.

THE EFFECT OF MICROGRAVITY ON TWO STRAINS OF BIOFUEL PRODUCING ALGAE WITH IMPLICATIONS FOR THE PRODUCTION OF RENEWABLE FUELS IN SPACE-BASED APPLICATIONS

Chatfield High School (Littleton, CO)

Implementation Partner: NanoRacks

Algae can produce both fats and hydrogen, which can each be used as fuel sources on Earth and potentially in space. NanoRacks-National Design Challenge-Chatfield High School-The Effect of Microgravity on Two Strains of Biofuel Producing Algae with Implications for the Production of Renewable Fuels in Space Based Applications (NanoRacks-NDC-CHS-The Green Machine) studies two algae species to determine whether they still produce hydrogen and store fats while growing in microgravity. Results from this student-designed investigation improve efforts to produce a sustainable biofuel in space, as well as remove carbon dioxide from crew quarters.

TOMATOSPHERE-II

Ann Jorss, First the Seed Foundation (Alexandria, VA)

Implementation Partner: CASIS

Tomatosphere is a hands-on student research experience with a standards-based curriculum guide that provides students the opportunity to investigate, create, test, and evaluate a solution for a real world case study. Tomatosphere provides information about how spaceflight affects seed and plant growth and which type of seed is likely to be most suitable for long duration spaceflight. It also exposes students to space research, inspiring the next generation of space explorers. It is particularly valuable in urban school settings where students have little connection to agriculture. In its 15-year existence, the program has reached approximately 3.3 million students.

VALLEY CHRISTIAN HIGH SCHOOL STUDENT EXPERIMENTS

Valley Christian High School (San Jose, CA), in partnership with other high schools throughout the world

Implementation Partner: NanoRacks

Students at Valley Christian High School (VCHS) have a rich history of sending investigations to the ISS through its launch partner, NanoRacks. On SpaceX CRS-11, students from VCHS have partnered with other students from across the world to send 12 total experiments to the ISS National Laboratory. Investigations will range from investigating high quality food nutrients, to the fermentation of microbes, to even an investigation monitoring the growth of a special bacterial strain. The program VCHS has developed with NanoRacks allows students the opportunity to not only conceive a flight project, but learn, understand, and implement the engineering required for a successful experiment in microgravity.

Thus far in 2017, the ISS National Lab has sponsored over 75 separate experiments that have reached the station. This launch manifest adds to an impressive list of experiments from previous missions in 2017 to include; stem cell studies, cell culturing, protein crystal growth, external platform payloads, student experiments, Earth observation and remote sensing. To learn more about those investigations and other station research, visit http://www.spacestationresearch.com.

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About CASIS: The Center for Advancement of Science in Space (CASIS) is the non-profit organization selected to manage the ISS National Laboratory with a focus on enabling a new era of space research to improve life onEarth. In this innovative role, CASIS promotes and brokers a diverse range of research inlife sciences,physical sciences,remote sensing,technology development,andeducation.

Since 2011, the ISS National Lab portfolio has included hundreds of novel research projects spanning multiple scientific disciplines, all with the intention of benefitting life on Earth.. Working together with NASA, CASIS aims to advance the nations leadership in commercial space, pursue groundbreaking science not possible on Earth, and leverage the space station to inspire the next generation.

About the ISS National Laboratory: In 2005, Congress designated the U.S. portion of the International Space Station as the nation’s newest national laboratory to maximize its use for improving life on Earth, promoting collaboration among diverse users, and advancing STEM education. This unique laboratory environment is available for use by other U.S. government agencies and by academic and private institutions, providing access to the permanent microgravity setting, vantage point in low Earth orbit, and varied environments of space.

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Attachments:

http://www.globenewswire.com/NewsRoom/AttachmentNg/d48a20de-af55-4274-8ce8-dd876e62a78d

Attachments:

A photo accompanying this announcement is available at http://www.globenewswire.com/NewsRoom/AttachmentNg/565f968b-ad65-42c2-be54-97423c9dbcba

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Over 40 U.S. National Laboratory Sponsored Experiments on SpaceX CRS-11 Destined for the International Space … – GlobeNewswire (press release)

Dissecting the Press Release for a Failed Stem Cell Trial – MedPage Today

Stem cells have never been shown to have any clinical benefit in patients with heart disease. But there is mounting anecdotal evidence that they may have serious adverse effects on the reasoning and objectivity of the medical researchers, biotechnology executives and investors who get sucked into their orbit.

The most recent example is the ALLSTAR trial, which crashed and burned last week. In a press release, Capricor Therapeutics announced that “a pre-specified administrative interim analysis performed on six-month follow-up data from the ALLSTAR Trial, an ongoing randomized, double-blind, placebo-controlled, 142-patient Phase II clinical trial of CAP-1002 (allogeneic cardiosphere-derived cells) in adults who have experienced a large heart attack with residual cardiac dysfunction, has demonstrated a low probability (futility) of achieving a statistically-significant difference in the 12-month primary efficacy endpoint of percent change from baseline infarct size as a percent of left ventricular mass, measured by cardiac magnetic resonance imaging (MRI).”

But in the press release the trial investigators and company officials never even mention the distinct possibility that their product doesn’t work. Instead, they do everything they can to spin all sorts of positive views of the results.

For instance, co-principal investigator Raj Makkar, of the Cedars-Sinai Heart Institute, is quoted in the press release as saying that “we are disappointed that the ALLSTAR six-month data did not demonstrate evidence of scar size improvement with CAP-1002, given the robust findings demonstrated on this measure in the randomized Phase I CADUCEUS clinical trial of cardiosphere-derived cells in a similar patient population.”

But Makkar conveniently ignores the fact that the earlier trial missed its most important endpoint, improvement in left ventricular ejection fraction and it was on this basis that infarct size was the main goal of ALLSTAR. In other words, infarct size was a cherry picked endpoint in ALLSTAR only because the preferred endpoint didn’t work out in the earlier trial.

In the press release Makkar tries to explain away the failure: “We believe it is important to note that the observed improvements in scar size in the placebo group are markedly inconsistent with the well-established natural history of this disease process. It is certainly possible that, for a variety of reasons, the greater number of sites involved in the conduct of ALLSTAR contributed to an increase in variability seen in the scar measurements as determined by MRI.”

Makkar doesn’t elaborate on any of the “variety of reasons” why “the greater number of sites” leads to the negative finding. In general, in a well conducted trial more sites and more patients should lead to greater reliability of the finding, not less. Makkar appears to be implying that he and his group are the only ones who are able to see the benefits for which they are looking. This should raise all sorts of red flags.

Indeed, everyone quoted in the press release including Makkar has a strong motivation for the therapy to succeed.

First, they are all closely connected. There is not even the pretense of an outside, objective perspective. Linda Marbn is the president and CEO of Capricor. She is also married to Eduardo Marbn, a prominent researcher and the founder of Capricor. Eduardo Marbn is also the director of the Cedars-Sinai Heart Institute. The two co-principal investigators of ALLSTAR are Makkar and Timothy Henry, both of whom work under Marbn at Cedars Sinai. Makkar is the associate director of interventional technologies in the Heart Institute and Henry heads the division of cardiology.

The conflicts are even more deep rooted. The home institution for Marbn and the other investigators, Cedars-Sinai, has a significant financial stake in Capricor.

Henry also sought and found positive signs in the trial. “We are encouraged to see reductions in left ventricular volume measures in the CAP-1002 treated patients, an important indicator of reverse remodeling of the heart. These findings support the biological activity of CAP-1002.” But when you miss your major prespecified endpoint any secondary findings must be considered exploratory at best. Given the dismal results of all previous stem cell trials in cardiology extreme skepticism is warranted in this sort of analysis. But Henry, a veteran stem cell researcher, doesn’t express any such caution.

Everyone involved is highly motivated to see this as a success. They all have rose-tinted glasses. Who among any of these major players has any motivation to view the company, the products, or the underlying science objectively or critically?

This is the nearly inevitable danger when there’s no outside critical perspective, and it is especially dangerous in small studies without rigorous controls. The investigators are motivated to grasp at the straws, which in this case means cherry picking their endpoints.

A New Target

Despite the optimistic spin, in its press release the company indicated it would likely abandon the cardiac indication for CAP-1002 in favor of a new indication in boys and young men with Duchenne muscular dystrophy (DMD). The company recently reported positive interim information from a 25-patient phase I/II trial in this population.

“Although we are disappointed, the favorable safety profile demonstrated by CAP-1002 in ALLSTAR supports the prospect of its chronic, repeat administration in patients with Duchenne muscular dystrophy. Also, the potent anti-inflammatory properties of CAP-1002 may be well-suited to mitigate DMD progression, for which chronic inflammation is believed to play a causative role,” said Linda Marbn.

Given the history, of this therapy in particular and of stem cells in general, extreme caution is warranted.

An important motivating factor for Capricor may well be that the regulatory barrier is much lower for a DMD indication than for a cardiac indication, as demonstrated last year by the approval of Sarepta’s DMD drug with little or no evidence of clinical benefit. Capricor plans to ask the FDA to grant Breakthrough Therapy or Regenerative Medicine Advanced Technology status for the new CAP-1002 indication.

A String of Failures

Hundreds of millions of dollars have been spent on cardiac stem cell research over nearly two decades now without any sign of success or progress.

Recently, as reported by Retraction Watch, in the latest installment of a long-running scandal, Brigham and Women’s Hospital agreed to give back $10 million to the US government in response to fraud charges against 3 prominent stem cell researchers, Piero Anversa, Annarosa Leri, and Jan Kajstura. Anversa, it should be noted, practically invented the field of cardiac stem cell therapy when he first reported that cardiac cells were capable of regeneration.

I recently criticized another prominent leader in the field, Roberto Bolli, for arguing that the proper response to this dismal record is more stem cell therapy, not less. With absolutely no concrete evidence, he argued that the single dose of cells used in virtually all previous stem cell therapy trials should be replaced with repeated doses of stem cells.

ALLSTAR is only the latest in a string of failures for stem cell therapies. Isn’t it time for people in the field to acknowledge that after decades of failure the field is not going to move forward?

Previous Stem Cell Stories:

2017-05-22T14:00:00-0400

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Dissecting the Press Release for a Failed Stem Cell Trial – MedPage Today

Heart Disease | Harvard Stem Cell Institute (HSCI)

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

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

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

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

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

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

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

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

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

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

Read more:
Heart Disease | Harvard Stem Cell Institute (HSCI)

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

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)

Robot hearts: medicine’s new frontier – The Guardian

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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Continued here:
Robot hearts: medicine’s new frontier – The Guardian

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

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

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

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

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

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

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

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

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

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