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Researchers use stem cells to regenerate the external layer of a human heart

By Stefanie Tomlinson January 11, 2017 UNIVERSITY PARK, Pa. — A process using human stem cells can generate the cells that cover the external surface of a human heart — epicardium cells — 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 Wnt signaling pathway, they become myocardium muscle cells," said Xiaojun Lance Lian, assistant professor of biomedical engineering and biology, who is leading the study at Penn State. Myocardium, the middle of the heart’s 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 didn't know what that information was," said Lian. "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." The group's results, published in Nature Biomedical Engineering, bring them 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 heart's inner layer), and we are making progress on that," said Lian. The group's method of generating epicardium cells could be useful in clinical applications, for patients who suffer a heart attack. According to the [...]

New Drug Could Help Prevent Artery Disease in High-risk Patients

A recent study by researchers at the University of Missouri School of Medicine has shown that a protein inhibitor drug prevents these blockages, and could be a new therapeutic approach to prevent heart attack, stroke and other diseases caused by blocked blood vessels. Dec. 21, 2016- According to the American Heart Association, approximately 2,200 Americans die each day from heart attacks, strokes and other cardiovascular diseases. The most common cause is blocked blood vessels that can no longer supply oxygen and nutrients to the heart and brain. A recent study by researchers at the University of Missouri School of Medicine has shown that a protein inhibitor drug prevents these blockages, and could be a new therapeutic approach to prevent heart attack, stroke and other diseases caused by blocked blood vessels. William Fay, MD "Arteries are living hoses that narrow and enlarge in order to regulate blood flow to organs and muscles," said William Fay, MD, the J.W. and Lois Winifred Stafford Distinguished Chair in Diabetes and Cardiovascular Research at the MU School of Medicine and senior author of the study. "Smooth muscle cells in the artery regulate blood flow by constricting and relaxing. However, when chronic inflammation occurs in a blood vessel - typically in response to diabetes, high cholesterol and cigarette smoking - the smooth muscle cells in the walls of arteries change their behavior. They gradually accumulate inside the artery and narrow the blood vessel. In the case of coronary arteries, which supply blood to heart muscle cells, this process produces blockages that can lead to a heart attack." Plasminogen activator inhibitor-1, or PAI-1, is a naturally occurring protein within blood vessels that controls cell migration. With diseases such as diabetes and obesity, [...]

Scientists Create Heart Cells Better, Faster, Stronger

By Dana G. Smith, PhD / Gladstone News / November 10, 2016 Tamer Mohamed, PhD, (left) and Deepak Srivastava, MD, identified two chemicals that improve the speed, quantity, and quality of direct cardiac reprogramming, bringing the technology one step closer to regenerating damaged hearts in patients. [Photo: Chris Goodfellow, Gladstone Institutes] Scientists at the Gladstone Institutes identified two chemicals that improve their ability to transform scar tissue in a heart into healthy, beating heart muscle. The new discovery advances efforts to find new and effective treatments for heart failure. Heart failure afflicts 5.7 million Americans, costs the country $30.7 billion every year, and has no cures. When heart muscle is damaged, the body is unable to repair the dead or injured cells. Gladstone scientists are exploring cellular reprogramming—turning one type of adult cell into another—in the heart as a way to regenerate muscle cells in the hopes of treating, and ultimately curing, heart failure. It takes only three transcription factors—proteins that turn genes on or off in a cell—to reprogram connective tissue cells into heart muscle cells in a mouse. After a heart attack, connective tissue forms scar tissue at the site of the injury, contributing to heart failure. The three factors, Gata4, Mef2c, and Tbx5 (GMT), work together to turn heart genes on in these cells and turn other genes off, effectively regenerating a damaged heart with its own cells. But the method is not foolproof—typically, only ten percent of cells fully convert from scar tissue to muscle. This heart muscle cell was reprogrammed from scar tissue in a mouse heart after a heart attack. [Image: Tamer Mohamed, Gladstone Institutes] In the new study, published in Circulation, Gladstone scientists tested 5500 chemicals to try [...]

Scientists find culprit responsible for calcified blood vessels in kidney disease

Stem cell finding informs research to prevent hardening of arteries By Julia Evangelou Strait September 8, 2016 A new study indicates that stem cells called Gli1 cells (shown in red) are responsible for depositing calcium in the arteries, increasing the risk of atherosclerosis. Over time, the condition can lead to cardiovascular disease and is especially common in patients with chronic kidney disease. The research may help scientists find ways to prevent hardening of arteries. (Image: Humphries Lab)Scientists have implicated a type of stem cell in the calcification of blood vessels that is common in patients with chronic kidney disease. The research will guide future studies into ways to block minerals from building up inside blood vessels and exacerbating atherosclerosis, the hardening of the arteries. The study, led by researchers at Washington University School of Medicine in St. Louis, appears Sept. 8 in the journal Cell Stem Cell. “In the past, this calcification process was viewed as passive — just mineral deposits that stick to the walls of vessels, like minerals sticking to the walls of water pipes,” said senior author Benjamin D. Humphreys, MD, PhD, director of the Division of Nephrology and an associate professor of medicine. “More recently, we’ve learned that calcification is an active process directed by cells. But there has been a lot of controversy over which cells are responsible and where they come from.” The cells implicated in clogging up blood vessels with mineral deposits live in the outer layer of arteries and are called Gli1 positive stem cells, according to the study. Because they are adult stem cells, Gli1 cells have the potential to become different types of connective tissues, including smooth muscle, fat and bone. Humphreys and his colleagues [...]

Researchers are Pioneering Tools for Heart Regeneration

Tue, 08/09/2016 - 9:45am by University of Houston A team of developmental biologists at the University of Houston have uncovered new regulators of heart formation that are easier to deliver into human bodies, and thus have a shorter path to clinical use. Source: Courtesy of Yu Liu Cardiovascular diseases are the leading cause of death in the U.S. With one in every four deaths occurring each year, the five-year survival rate after a heart attack is worse than most cancers. A big part of the problem is the inability of the human heart to effectively repair itself after injury. A team of University of Houston researchers is trying to change that. Physicians and biologists are developing strategies to help regenerate heart muscle cell formation. Among them are developmental biologists in UH's College of Natural Sciences and Mathematics, whose work has added novel, powerful tools to achieve this. Their findings are published in the Aug. 8 early edition of the Proceedings of the National Academy of Sciences(PNAS), one of the world's most-cited multidisciplinary scientific journals. The human heart is an organ that doesn't regenerate, and the number of heart muscle cells drops as a person ages. Cells lost during injuries, such as from a heart attack, are gradually replaced by connective tissue, a process called fibrosis. This leads to the loss of pump function, which is the underlying reason cardiovascular diseases are as deadly as cancers. "We have uncovered new regulators of heart formation," said assistant professor of biochemistry Yu Liu, one of the lead authors of the study. "Compared to most others, these new regulators, which are a small RNA species called microRNAs, act early in the multistep heart formation process. They are easier to deliver into [...]

Genetic error that increases risk of aortic rupture identified

Study sheds light on unexplained enlargement, weakening of aorta By Julia Evangelou Strait July 18, 2016 In young people, aortic aneurysms are most often caused by an inherited condition,such as Marfan syndrome. Standard genetic tests often pinpoint the reason for inheritedaortic disease, but some cases remain medical mysteries. A new study adds lysyl oxidaseto the standard list of genes that should be tested when a young person shows an enlarged aorta.Lysyl oxidase helps maintain structural integrity of blood vessels. (Image: Bruce Blaus) A study led by Washington University School of Medicine in St. Louis, in collaboration with Brigham and Women’s Hospital in Boston, has identified a genetic error that weakens the aorta, placing patients with this and similar errors at high risk of aortic aneurysms and ruptures. The findings will help diagnose, monitor and treat patients with aortic disease not caused by well-known conditions, such as Marfan syndrome and other genetic mutations known to disrupt connective tissues. The study appears July 18 in the Proceedings of the National Academy of Sciences. Working with the Brigham Genomic Medicine Program, the researchers identified the mutation in a family with a history of aortic disease but no known genetic reason for the condition. The error is in a gene called lysyl oxidase (LOX), which Washington University researchers have shown is responsible for connecting networks of tissue fibers that make up blood vessels. The aorta is the body’s largest artery that carries blood from the heart to the rest of the body. A lifetime of smoking and poor cardiovascular health can lead to aortic aneurysms in older adults. But bulging and tearing of the aorta in a young person is most often due to an inherited condition. A number [...]

Micro heart muscle created from stem cells

Posted: Apr 21, 2016   (Nanowerk News) Scientists at the Gladstone Institutes have invented a new way to create three-dimensional human heart tissue from stem cells ("Miniaturized iPS-Cell-Derived Cardiac Muscles for Physiologically Relevant Drug Response Analyses"). The tissue can be used to model disease and test drugs, and it opens the door for a precision medicine approach to treating heart disease. Although there are existing techniques to make three-dimensional tissues from heart cells, the new method dramatically reduces the number of cells needed, making it an easier, cheaper, and more efficient system. "We have bioengineered micro-scale heart tissues with a method that can easily be reproduced, which will enable scientists in stem cell biology and the drug industry to study heart cells in their proper context," said first author Nathaniel Huebsch, PhD, a postdoctoral fellow in the Conklin lab at Gladstone. "In turn, this will enhance our ability to discover treatments for heart disease." Creating heart cells from induced pluripotent stem cells (iPSCs) that are derived from a patient's skin cells enables scientists to study and test drugs on that patient's specific disease. However, cells made from iPSCs are relatively immature, resembling heart cells in an embryo more than cells in an adult. As such, these cells are inadequate for drug testing because they do not properly predict how a drug will affect adult heart cells. Additionally, heart cells created from iPSCs are challenging to make and work with, so creating large quantities can be difficult. Therefore, the fewer cells needed, the better. The micro heart muscle addresses both of these concerns. Forcing the cells to organize and stretch into three-dimensional tissue helps spur development and coaxes them into resembling more mature cells that can [...]

Stem cell therapy ‘halves number of heart failure deaths’

April 11, 2016 Spectator Health reporter Injecting adult stem cells into the heart could potentially halve the number of deaths from heart failure, a study has suggested. The study, published in the Lancet, found that patients who received the treatment had a 37 per cent lower rate of death and hospitalisation for heart failure-related problems. The study involved 126 patients from hospitals across America. Sixty patients were injected with stem cells while 66 were injected with a placebo. The procedure took two hours and most patients were discharged a day after surgery. In the non-placebo group, stem cells were taken from the patients’ bone marrow, grown in culture, and then injected directly into the patients’ hearts. In the stem cell therapy group 3.4 per cent of the patients died and 51.7 per cent were hospitalised, compared to 13.7 per cent and 82.4 per cent respectively in the group that received a placebo. Dr Amit Patel, director of Cardiovascular Regenerative Medicine at the University of Utah, said: ‘For the last 15 years everyone has been talking about cell therapy and what it can do. These results suggest that it really works.’ He said it works either because it ‘slows down or reverses the rate of progression of disease’. Rather than increasing the number of muscle cells or blood vessels in the heart, he said, it likely makes the existing cells work better. However, the study authors say they found only a small overall improvement in heart function. The researchers are hoping to start a larger phase 3 clinical trial involving more heart failure patients. About 900,000 people in Britain live with heart failure, which blocks blood vessels and reduces blood supply to the body. Instant analysis [...]

Functional Heart Muscle Regenerated in Decellularized Human Hearts

Mon, 03/14/2016 - 12:00pm Massachusetts General Hospital A partially recellularized human whole-heart cardiac scaffold, reseeded with human cardiomyocytes derived from induced pluripotent stem cells, being cultured in a bioreactor that delivers a nutrient solution and replicates some of the environmental conditions around a living heart. (Credit: Bernhard Jank, M.D./Ott Lab/ Center for Regenerative Medicin/, Massachusetts General Hospital)Massachusetts General Hospital (MGH) researchers have taken some initial steps toward the creation of bioengineered human hearts using donor hearts stripped of components that would generate an immune response and cardiac muscle cells generated from induced pluripotent stem cells (iPSCs), which could come from a potential recipient. The investigators described their accomplishments - which include developing an automated bioreactor system capable of supporting a whole human heart during the recellularization process -- earlier this year in Circulation Research."Generating functional cardiac tissue involves meeting several challenges," said Jacques Guyette, Ph.D., of the MGH Center for Regenerative Medicine (CRM), lead author of the report. "These include providing a structural scaffold that is able to support cardiac function, a supply of specialized cardiac cells, and a supportive environment in which cells can repopulate the scaffold to form mature tissue capable of handling complex cardiac functions." The research team is led by Harald Ott, M.D., of the MGH CRM and the Department of Surgery, senior author of the paper. In 2008, Ott developed a procedure for stripping the living cells from a donor organ with a detergent solution and then repopulating the remaining extracellular matrix scaffold with organ-appropriate types of cells. Since then his team has used the approach to generate functional rat kidneys and lungs and has decellularized large-animal hearts, lungs and kidneys. This report is the first to conduct a detailed analysis [...]

‘Broken’ heart breakthrough: researchers reprogram cells to better battle heart failure

UNC School of Medicine scientists overcame a significant barrier to convert scar-making fibroblasts into living, beating cardiomyocytes. Media contact: Mark Derewicz March 3, 2016 CHAPEL HILL, N.C. – Patients with heart failure often have a buildup of scar tissue that leads to a gradual loss of heart function. In a new study published today in the journal Cell Stem Cell, researchers from the University of North Carolina School of Medicine report significant progress toward a novel approach that could shrink the amount of heart scar tissue while replenishing the supply of healthy heart muscle. “Our past work brought hope that we could one day improve heart function in people with heart failure by converting scar tissue into beating heart muscle,” said Li Qian, PhD, assistant professor of pathology and laboratory medicine and the study’s senior author. “But that was more of a proof-of-principle study, and the conversion rate was quite low. Now we have found the barrier to conversion, and by removing it, we have been able to significantly increase the yield of muscle-like cells.” Heart failure has no cure and currently affects an estimated 5.7 million people in the United States. Common symptoms include shortness of breath, fatigue, and swelling, all of which often worsen as the heart weakens over time. “Our hope is that this approach could extend the lives of people with heart failure and markedly improve their quality of life in the future,” said Qian, who is also a member of the McAllister Heart Institute at UNC. In 2012, Qian and her colleagues created a “cocktail” of proteins capable of converting fibroblasts, which create scar tissue, into cardiomyocytes – heart muscle cells that beat on their own exactly the way regular heart [...]