Discovery of Stem Cells in Muscle Could Advance Development of Regenerative Therapies
8 Jun, 2007 04:13 pm
Stem cells provide the starting material for the development and repair of every organ and tissue in the body and they are present in all stages of life. While some stem cells are highly flexible, being able to give rise to many different types of tissue, other are much more restricted in their potential. Now, Canadian researchers have revealed that a population of cells in muscle tissue called satellite cells is in fact composed of two populations - one that can only give rise to new muscle tissue and one that appears to be much more flexible.
"We found that 90 per cent of satellite cells are committed to becoming muscle and 10 per cent have the characteristics normally attributed to stem cells," said Dr. Rudnicki, of the Sprott Centre for Stem Cell Research in Ottawa. "It has not been shown yet, but these muscle stem cells may even have the capacity to make other tissues, such as bone and fat."
As we walk, run, lift and stretch throughout the day, satellite cells help us repair minor muscle tears and build new muscle mass. Dr. Rudnicki's group observed that while all satellite cells express a gene called Pax7, only those cells committed to becoming muscle expressed another gene called Myf5. They bred a special strain of mice in which all satellite cells that had ever expressed Myf5 were labeled in yellow. This system allowed them to easily visualize satellite cell division in muscle tissue and distinguish between the two populations.
Under the microscope, satellite cells can be found in a special niche in muscle tissue, attached to the collagen matrix that surrounds muscle fibres. Dr. Rudnicki's group observed that when satellite cells that don't express Myf5 divide, their daughter cells remain attached to the collagen matrix and remain satellite stem cells. However when cells that do express Myf5 divide, their daughters move away from the matrix and eventually become new muscle fibres.
"We found that transplantation of the subpopulation of satellite cells that don't express Myf5 results in extensive repopulation of the satellite stem cell niche, said Dr. Rudnicki. "Overall these cells have a much greater potential for engraftment than the other population of satellite cells that do express Myf5."
These results are considered a significant step in the development of stem cell-based therapies for degenerative muscle diseases. While some work will now go into isolating these stem cells in human muscle tissue and developing ways to expand them for transplantation studies, Dr. Rudnicki is primarily interested in learning more about how these stem cells divide in order to eventually develop drugs that could affect the process.
"If we can identify the genetic switch that causes a satellite stem cell to either give rise to another stem cell or a muscle cell, we could possibly develop drugs to flip that switch and help people restore muscle stem cell reservoirs that have been depleted by diseases such as Duchenne muscular dystrophy. The discovery also raises the possibility of preventing the normal muscle deterioration that happens with old age," noted Dr. Rudnicki.
This research was published in the June 1, 2007 edition of the scientific journal Cell. It was funded by the Canadian Institute of Health Research, the National Institutes of Health and the Muscular Dystrophy Association. Dr. Rudnicki's laboratory at the Sprott Centre for Stem cell Research is part of the Ottawa Health Research Institute, the research arm of The Ottawa Hospital, affiliated with the University of Ottawa.
Kuang S., et al., Asymmetric Self-Renewal and Commitment of Satellite Stem Cells in Muscle, Cell, 01 June 2007