Research supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) has identified important differences in cells that play a key role in the growth, maintenance and repair of muscle tissue. The finding could potentially lead to a better understanding of and improved treatments for degenerative neuromuscular diseases such as muscular dystrophy.
The cells, called satellite cells, reside in the space between the fibers and collagen that make up mature skeletal muscle. Until now, researchers had assumed that all of these satellite cells had similar properties and followed the same developmental path to becoming mature muscle. But the new research provides evidence that satellite cells exist as two distinct populations: committed progenitor cells, which are destined to become muscle cells and have a limited lifespan, and satellite stem cells, which can undergo self-renewal as well as repopulate the satellite cell niche.
The research also shows that the type of path a satellite stem cell takes after cell division is influenced partially by the orientation of the new cells relative to the muscle fiber, says Michael A. Rudnicki, Ph.D., senior scientist and director of the Program in Regenerative Medicine at the Ottawa Health Research Institute and lead author of the new research published in the June 1, 2007, issue of Cell . When division occurred parallel to the muscle fiber, the resulting pair of daughter cells remained stem cells; however, when division occurred perpendicular to the muscle fiber, the resulting daughter cells differed: the one in contact with the muscle fiber became a progenitor cell, while the one in contact with the collagen matrix remained a stem cell.
Moreover, when transplanted into mice that lacked satellite cells, the uncommitted satellite stem cells behaved much like other stem cells, says Rudnicki. "Some rapidly filled the vacant space and began to convert to progenitor cells and integrate into the muscle, while others continued to produce uncommitted satellite stem cells that could be tapped into later if more muscle cells were needed," he says. When committed progenitor cells were transplanted, however, most developed into more mature muscle cells or died.
Dr. Rudnicki says this finding provides a new avenue for researchers to explore as they search for therapies that can help people who have, or are at high risk for developing, degenerative neuromuscular diseases. "One of the phenomena in Duchenne's muscular dystrophy, for example, is that satellite cells are progressively lost, and we haven't understood why that is," he says. "We need to look at them with this new knowledge to understand what is happening to these satellite stem cells."
By better understanding the cells and what goes wrong with them, scientists may be able to develop pharmacologic methods to enhance their self-renewal, thereby increasing their numbers, Rudnicki says. "Alternatively, if we could develop methods for culturing these specific cells, then perhaps transplant becomes a viable option."
The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases a part of the Department of Health and Human Services' National Institutes of Health, is to support research into the causes, treatment and prevention of arthritis and musculoskeletal and skin diseases; the training of basic and clinical scientists to carry out this research; and the dissemination of information on research progress in these diseases. For more information about NIAMS, call the information clearinghouse at (301) 495-4484 or (877) 22-NIAMS (free call) or visit the NIAMS Web site at http://www.niams.nih.gov/
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Kuang S, et al . Asymmetric self-renewal and commitment of satellite stem cells in muscle. Cell . 2007:129(5):999-1010.