Researchers have recently discovered that a subpopulation of muscle-generating stem cells in adult mice can replicate themselves up to 300 times over a six-month period. The finding, they believe, demonstrates the feasibility of generating large quantities of adult skeletal muscle stem cells required for use in clinical applications, such as transplantation into the damaged muscles of people with muscular dystrophy. Their work was partly supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS).
The research was carried out by Johnny Huard, Ph.D., and his colleagues at Children's Hospital of Pittsburgh and the University of Pittsburgh. The scientists showed that a subpopulation of adult muscle stem cells, obtained from skeletal muscles of normal mice, could undergo up to 300 population doublings (PDs) under laboratory conditions. A population doubling is a one-hundred percent increase in the total number of cells in a culture. In theory, after 300 PDs, one single cell can eventually give rise to 10100 cells.
More importantly, the researchers successfully showed that these cells were able to maintain their ability to regenerate skeletal muscles when expanded to the level of 200 PDs. When expanded beyond 200 PDs, however, the cells lost some of their ability to regenerate muscles and started to demonstrate some of the characteristics of cancer cells. The causes of these changes are not well understood, according to the researchers.
The scientists also genetically marked some muscle stem cells obtained from normal mice, and transplanted them into the muscles of "mdx mice," an animal model of muscular dystrophy. Two weeks later, the scientists were able to remove the marked stem cells from the mdx mice that had received the transplantation. Once these marked stem cells were retrieved, they were expanded (multiplied) under laboratory conditions, and then transplanted into muscles of another group of mdx mice. Two weeks after the second transplantation, the same kind of genetically marked cells were again successfully retrieved from the mouse muscles. Successful serial transplantations of stem cells in two groups of mdx mice suggest that this type of stem cells can renew itself in the muscles of living mice.
Dr. Huard and his colleagues suggested that more research needs to be done before using adult muscle stem cell therapy in MD patients. For instance, the biological behaviors of stem cells need to be further studied. Another issue of importance is the potential of highly expanded muscle stem cells to become cancerous. These issues are among the many hurdles ahead to overcome before closing the gap between laboratory bench discovery and bedside application.
Muscular dystrophy (MD) is a collection of genetic disorders in which muscle cells become progressively more damaged and die. The most common and severe type of MD is Duchenne muscular dystrophy (DMD), characterized by the absence of dystrophin, a protein involved in maintaining the integrity of muscle fiber.
Although enormous progress has been made in elucidating the molecular basis of MD, there is currently no cure for the disorders. Several different methods have been studied for treating MD, including gene therapy, pharmacological therapy and cell therapy. Several types of adult stem cells are currently being studied to see if they are capable of regenerating skeletal muscles.
Other support for this research came from the Muscular Dystrophy Association, Children's Hospital of Pittsburgh and the University of Pittsburgh.
The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), 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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Deasy BM, et al.. Long-term self-renewal of postnatal muscle-derived stem cells. Mol Biol Cell. 2005;16(7):3323-33.