Scientists take aging cardiac stem cells out of semiretirement to improve stem cell therapyOctober 03, 2016
AUGUSTA, Ga. (Oct. 3, 2016) - With age, the chromosomes of our cardiac stem cells compress as they move into a state of safe, semiretirement.
The typically long, coiled strand of DNA inside each youthful stem cell gets shorter and dense as we age, literally leaving less room for it to be cut or otherwise damaged and die, said Dr. Yaoliang Tang, cardiovascular researcher in the Vascular Biology Center at the Medical College of Georgia at Augusta University.
"If you condense it, it's less responsive," Tang said. "The cells look like they fall asleep," he said of a scenario that plays out in aging stem cells all over the body. But that protective, condensing strategy also means a preconditioning treatment that will help stem cells make new blood vessels for starving heart muscle doesn't have good access either.
Tang is principal investigator on a new $1.5 million grant from the National Heart, Lung and Blood Institute that is enabling him to restore the youthful length to the DNA just long enough to his get preconditioning therapy inside. Then, his research team will see what that does to the stem cell's ability to revascularize heart muscle following a heart attack, improve heart function and possibly help avoid worsening disease.
"When the chromosome is open, it will make the cells wake up," Tang said. His early evidence suggests that the rejuvenated stem cells will respond better to a short period of hypoxia - or reduced oxygen levels - that encourages them to make things that are good for the ailing heart. This includes vascular endothelial growth factor, or VEGF, that will pave the inside of new blood vessels; endothelial nitric oxide synthase, or eNOS, that will help blood vessels dilate; and placental growth factor that is highly expressed in the embryo and will also aid development of new blood vessels, called angiogenesis.
With age, the number of cardiac stem cells - which can form a myriad of heart tissue from actual heart cells to the blood vessels that feed them - decreases. Inside those that remain, expression of the enzyme EZH2 goes way up, which appears to contribute to the cells' semiretirement. The drug DZnep, already used in patients to open up the DNA of cancer cells and make them more vulnerable to cancer therapy, is one way to temporarily rouse the stem cells. Tang notes this shows there is a "druggable" target so his study findings should translate well to humans. MCG researchers also are using molecules called small interfering RNAs, or siRNAs, to ablate the enzyme EZH2 and see what happens.
Tang's goals include learning more about how EZH2 is regulated and how it in turn, essentially turns down the responsiveness of aging stem cells. While his next round of studies will likely follow how many actual new heart cells are made by the temporarily rejuvenated stem cells, this time his focus is the growth of new blood vessels that will help reperfuse the ailing heart and would be essential to survival of any new heart cells.
His team will follow the mice one to two months to see what happens after cell transplantation, said Tang, noting that the response should be fairly rapid. Adding a fluorescent tag to the transplanted stem cells will enable them to see where the cells go, and sophisticated imaging technology will enable them to examine perfusion of the mice's working heart. In his early studies, Tang has already watched the aged chromosomes extend then retract when treated with DZnep. Now his team is doing studies in both younger and aged cardiac stem cells to enable continued comparison of the two populations. In fact, Tang is optimistic their approach will also enhance the efficiency of the younger cells as well.
Tang was first author on a 2009 paper in the journal Circulation Research that showed a period of hypoxia, or low-oxygen levels, prior to transplant improved the ability of transplanted cardiac stem cells to reach the ailing heart and improve heart function.
Inside the heart, stem cells are accustomed to oxygen levels that are about five times lower than the ones they will experience when taken out of the body in preparation for a transplant. His hypoxia preconditioning takes oxygen levels even lower, to embryonic levels, when stem cells were busy making entire organs. The low-oxygen environ appears to put the cells into action mode, activating the protein CXCR4, which in turn, activates signaling pathways that enable beneficial things like cell growth and division and work as a sort of homing system so the stem cells can find their way back to the heart after transplant.
Those first studies were done in a younger mouse model. But typically it's older patients who have heart attacks, and older stem cells, the researchers would find, were not as responsive to the hypoxia preconditioning, likely a reason that limited experience with cardiac stem cell transplants has not yielded the benefit to patients that laboratory studies would have indicated, Tang said.
Tang, an MD/PhD, who worked as a cardiac surgeon in China for more than a decade, says the cardiac stem cell therapy should one day be a good adjunct therapy for coronary bypass surgery patients and potential stand-alone therapy for patients with lesser ischemic heart disease or heart failure to rebuild the heart's microcirculation, perfusion and function. The technique of reopening the chromosomes of aged stem cells of all types could also improve the efficacy other types of stem cell therapies, Tang said.
Medical College of Georgia at Augusta University
Related Stem Cells Articles:
Researchers have identified a protein that must be present in order for mammary stem cells to perform their normal functions.
Researchers at Boston Children's Hospital have, for the first time, generated blood-forming stem cells in the lab using pluripotent stem cells, which can make virtually every cell type in the body.
Researchers have developed a new approach for growing and studying cells they hope one day will lead to curing lung diseases such as cystic fibrosis through 'personalized medicine.'
Generating mature and viable heart muscle cells from human or other animal stem cells has proven difficult for biologists.
DNA mutations in bone cells that support blood development can drive leukemia formation in nearby blood stem cells.
With age, the chromosomes of our cardiac stem cells compress as they move into a state of safe, semiretirement.
A team of researchers from the Medical University of South Carolina and elsewhere has found a better way to purify liver cells made from induced pluripotent stem cells.
International stem cell scientists, co-led in Canada by Dr. John Dick and in the Netherlands by Dr.
Signaling a potential new approach to treating diabetes, researchers at Washington University School of Medicine in St.
In a new Cell Reports paper, a team led by John P.
Related Stem Cells Reading:
Stem Cell Therapy: A Rising Tide: How Stem Cells Are Disrupting Medicine and Transforming Lives
by Neil H Riordan (Author)
Stem cells are the repair cells of your body. When there aren’t enough of them, or they aren’t working properly, chronic diseases can manifest and persist. From industry leaders, sport stars, and Hollywood icons to thousands of everyday, ordinary people, stem cell therapy has helped when standard medicine failed. Many of them had lost hope. These are their stories.
Neil H Riordan, author of MSC: Clinical Evidence Leading Medicine’s Next Frontier, the definitive textbook on clinical stem cell therapy, brings you an easy-to-read book about how and why stem cells work,... View Details
Stem Cells: An Insider's Guide
by Paul Knoepfler (Author)
Stem Cells: An Insider's Guide is an exciting new book that takes readers inside the world of stem cells guided by international stem cell expert, Dr. Paul Knoepfler. Stem cells are catalyzing a revolution in medicine. The book also tackles the exciting and hotly debated area of stem cell treatments that are capturing the public's imagination. In the future they may also transform how we age and reproduce. However, there are serious risks and ethical challenges, too. The author's goal with this insider's guide is to give readers the information needed to distinguish between the... View Details
The Stem Cell Revolution
by Mark Berman MD (Author), Elliot Lander MD (Contributor)
The book describes the journey into the growing arena of clinical stem cell therapy by highlighting not only the road that brought a team of physicians together but also real stories from a number of their patients that were given their health back through the magic of stem cell therapy. Your fat is loaded with stem cells that can be used now to treat and reverse a large number of inflammatory and degenerative conditions. Most people have no idea that these magical cells actually exist right within our bodies. They think that they must wait until Big Pharma or a university PhD manufactures... View Details
Stem Cells For Dummies
by Lawrence S.B. Goldstein (Author), Meg Schneider (Author)
The first authoritative yet accessible guide to this controversial topic
Stem Cell Research For Dummies offers a balanced, plain-English look at this politically charged topic, cutting away the hype and presenting the facts clearly for you, free from debate. It explains what stem cells are and what they do, the legalities of harvesting them and using them in research, the latest research findings from the U.S. and abroad, and the prospects for medical stem cell therapies in the short and long term.Explains the differences between adult stem cells and embryonic/umbilical... View Details
Stem Cells Are Everywhere
by Irv Weissman MD (Author)
An engaging introduction to stem cells for young scientists
How do you heal when you cut your skin or break a bone? How does your body keep making new blood or brain cells, or even second teeth? How does a plant keep growing larger? The answers lie in stem cells, which are found in every growing plant and animal. Keeping the subject simple enough for young readers, a pioneer of stem cell research explains cells, tissues, normal growth, what can go wrong, and how to fix it. View Details
Stem Cells: A Very Short Introduction
by Jonathan Slack (Author)
Embryonic stem cells have been hot-button topics in recent years, generating intense public interest as well as much confusion and misinformation. In this Very Short Introduction, leading authority Jonathan Slack offers a clear and informative overview of stem cells--what they are, what scientists do with them, what stem cell therapies are available today, and how they might be used in the future. Slack explains the difference between embryonic stem cells, which exist only in laboratory cultures, and tissue-specific stem cells, which exist in our bodies, and he discusses how... View Details
Stem Cells: A Short Course
by Rob Burgess (Author)
Stem Cells: A Short Course is a comprehensive text for students delving into the rapidly evolving discipline of stem cell research. Comprised of eight chapters, the text addresses all of the major facets and disciplines related to stem cell biology and research. A brief history of stem cell research serves as an introduction, followed by coverage of stem cell fundamentals; chapters then explore embryonic and fetal amniotic stem cells, adult stem cells, nuclear reprogramming, and cancer stem cells. The book concludes with chapters on stem cell applications, including the role of stem... View Details
The Stem Cell Secret: How to Activate and Regerate Your Stem Cells Naturally and Affordably
Stem Cells live in every cell in your entire body and are designed to repair and rejuvenate your organs and tissues. Our Stem Cells become less effective in healing over time and at times can become overwhelmed with disease. This book shows how to use nutrition, supplements and life style tips to activate your Stem Cells and allow them to heal your body. View Details
Essentials of Stem Cell Biology, Third Edition
by Robert Lanza (Editor), Anthony Atala (Editor)
First developed as an accessible abridgement of the successful Handbook of Stem Cells, Essentials of Stem Cell Biology serves the needs of the evolving population of scientists, researchers, practitioners, and students embracing the latest advances in stem cells. Representing the combined effort of 7 editors and more than 200 scholars and scientists whose pioneering work has defined our understanding of stem cells, this book combines the prerequisites for a general understanding of adult and embryonic stem cells with a presentation by the world's experts of the latest... View Details
Stem Cells: Promise and Reality
by Lygia V Pereira (Author)
Stem Cells: Promises and Reality will tell you everything you have always wanted to know about stem cells, but could not understand the field from elsewhere. Stem cells are the great therapeutic promise of the century, and this evolving field of research and medicine brings with it many legal, ethical and psychological issues that must be discussed by society as a whole. Written so as to be accessible to general readers as well as specialists, this book explains what stem cells are, and the different aspects of stem cell research and applications. The book will enable the reader to understand... View Details