Researchers find shortened telomeres linked to dysfunction in Duchenne muscular dystrophySeptember 07, 2017
PHILADELPHIA--Researchers from the Perelman School of Medicine at the University of Pennsylvania have made a discovery about muscular dystrophy disorders that suggest new possibilities for treatment. In a study published today online in Stem Cell Reports, researchers found that stem cells in the muscles of muscular dystrophy patients may, at an early age, lose their ability to regenerate new muscle, due to shortened telomeres.
Telomeres are tail-like chains of DNA at the ends of chromosomes that protect chromosomes during cell division. In many cell types, telomeres also serve as biological countdown clocks, being shortened with every cell division until their reduced length triggers the death of the cell or an inactive, non-dividing state called senescence. The team found that telomeres specifically in muscle stem cells are abnormally short in teenage boys with Duchenne Muscular Dystrophy (DMD), as well as in young mice with the same genetic disorder. The finding of shortened telomeres could help explain why prior research has found defects in the functions of muscle stem cells from muscular dystrophy patients.
"We found that in boys with DMD, the telomeres are so short that the muscle stem cells are probably exhausted," said the study's senior author, Foteini Mourkioti, PhD, an assistant professor of Orthopaedic Surgery and Cell and Developmental Biology, and co-director of the Musculoskeletal Regeneration Program in the Penn Institute for Regenerative Medicine. "Due to the DMD, their muscle stem cells are constantly repairing themselves, which means the telomeres are getting shorter at an accelerated rate, much earlier in life. Future therapies that prevent telomere loss and keep muscle stem cells viable might be able to slow the progress of disease and boost muscle regeneration in the patients."
Muscles tend to degenerate in muscular dystrophy disorders because the gene mutations that cause these disorders leave muscle fibers abnormally fragile, so that they are damaged even by ordinary physical activity. In principle, muscle stem cells could regenerate this lost muscle, thereby slowing or even stopping the disease process. But some scientists, including Mourkioti, have suspected that in muscular dystrophy the continuous cycles of muscle damage and repair--requiring near-constant cell division for the muscle stem cells--soon erode the regenerative capacities of muscle stem cells, by shortening their telomeres and inducing early death or senescence.
"The problem with trying to identify what is happening in DMD muscle stem cells is that we've lacked sufficient tools for measuring telomere length in these stem cells," Mourkioti said.
To enable their discovery in DMD patients, Mourkioti and colleagues developed a new stem cell telomere-measuring method, based on an existing technique called fluorescence in situ hybridization (FISH). Telomeres are made of one short sequence of DNA building blocks (TTAGGG) repeated over and over, and the new FISH-based method (MuQ-FISH) uses a fluorescent probe designed to stick specifically to that sequence. Longer telomeres accumulate more probes and fluoresce more brightly. The technique can be used with a microscope and electronic imaging equipment to measure the lengths of telomeres within individual stem cells.
Mourkioti and her team initially used their new technique to show that the telomeres of muscle stem cells are about the same length in healthy lab mice, whether the mice are young or old. In contrast, the scientists found that in young mice with a severe DMD-like disorder as well as in several teenage patients with DMD, muscle stem cells on average had abnormally shortened telomeres. Other non-stem muscle cells in the DMD patients had normal telomere lengths.
The findings suggest that telomere-shortening specifically in muscle stem cells is a factor in the progressive muscle weakening and wasting seen in muscular dystrophy patients. That, in turn, suggests that gene therapy and other treatments now being developed for muscular dystrophies might be more beneficial if administered before muscle stem cells have lost their muscle-regenerating abilities. The findings also point to the possibility that future treatments to block the shortening of telomeres in muscle stem cells might be able to slow or even stop the disease. Mourkioti and colleagues now plan to employ their new method to help them find such a treatment, with an eye toward early intervention, when these stem cells are still capable of making new muscle.
"We are now looking for signaling pathways that affect telomere length in muscle stem cells, so that in principle we can develop drugs to block those pathways and maintain telomere length," Mourkioti said. "Currently very little is known about the factors that shorten or maintain telomeres."
There are about 30 distinct muscular dystrophy disorders, all caused by gene mutations that impair the integrity of muscle cells. The most common, DMD, is caused by mutations to a gene on the X-chromosome, and affects one of every fifteen hundred boys born in the United States. Milder muscular dystrophy disorders typically result in lifelong disability. More severe ones, such as DMD, eventually destroy the muscles needed for breathing, and reduce life expectancy to the mid-20s. At present, there is no specific treatment that can stop the progression of these diseases.
Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $6.7 billion enterprise.
The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 20 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $392 million awarded in the 2016 fiscal year.
The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center -- which are recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report -- Chester County Hospital; Lancaster General Health; Penn Wissahickon Hospice; and Pennsylvania Hospital -- the nation's first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine.
Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2016, Penn Medicine provided $393 million to benefit our community.
University of Pennsylvania School of Medicine
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
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 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
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: 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
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 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
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
The Science of Stem Cells
by Jonathan M. W. Slack (Author)
Introduces all of the essential cell biology and developmental biology background for the study of stem cells
This book gives you all the important information you need to become a stem cell scientist. It covers the characterization of cells, genetic techniques for modifying cells and organisms, tissue culture technology, transplantation immunology, properties of pluripotent and tissue specific stem cells and, in particular, the relevant aspects of mammalian developmental biology. It dispels many misconceptions about stem cells—especially that they can be miracle... View Details