The WNT7a protein increases proliferation of muscle repair cells, a finding that could have implications for MD treatment
In experiments in mice, Michael Rudnicki, an MDA grantee at the Sprott Center for Stem Cell Research at Ottawa Hospital Research Institute (OHRI), and colleagues, found the WNT7a protein stimulates muscle repair by causing proliferation (an increase in number) of "satellite stem cells." They say the protein probably operates similarly in humans. The findings were published June 5, 2009, in the journal Cell Stem Cell.
Satellite cells are located near mature muscle fibers in mice and humans and stay in a dormant state until called upon for repair work. In earlier experiments, Rudnicki found that some satellite cells function as stem cells and maintain overall numbers of satellite cells. He distinguished these from other satellite cells, which are in various stages on the road to becoming muscle tissue.
|MDA grantee Michael Rudnicki says the findings about WNT7a point the way toward developing drugs that can stimulate muscle repair.|
In muscular dystrophy, satellite cells are believed to become depleted quickly because tissue damage places great demands on them for repairs. Enhancing their numbers could slow the process of muscle degeneration, even in the face of disease.
"In muscle degenerative diseases, one of the big problems is thought to be that the muscles run out of repair cells," says Paul Muhlrad, a research program coordinator at MDA. "Rudnicki's laboratory has figured out the biochemical pathways the body uses to maintain the supply."
When the OHRI researchers injected genes for the WNT7a protein into muscle fibers in mice, they saw an increase in satellite stem cell numbers and enhanced muscle regeneration compared to what they saw in fibers that weren't treated this way.
"The identification of satellite stem cells and the pathways that regulate their function is an important advance in our knowledge," Rudnicki said. "We believe that this discovery points the way forward toward the development of new drugs that will stimulate muscle repair."
About Muscle Repair
Improving the ability of muscles to repair themselves in the face of disease has been a major focus of research by MDA for decades. This research is also relevant to muscles affected by aging and various types of injury.
In the early 1990s, MDA sponsored a number of clinical trials in which immature muscle cells called "myoblasts," taken from healthy relatives, were transplanted (injected) into the muscles of patients with Duchenne muscular dystrophy.
It was hoped that these cells would repair damaged muscle fibers in the patients. However, very little such repair was seen.
MDA researchers have since learned that most of the cells selected for transplantation were too far along in their maturation to join existing muscle tissue. They were not sufficiently flexible, or "stemlike," to perform the repair functions the scientists had hoped to see.
In the last two decades, Michael Rudnicki and other MDA-supported researchers have contributed much to the body of knowledge about muscle stem cells, satellite cells and myoblasts.
Satellite cells, they've found, can divide to form two new satellite cells, each with the potential to remain dormant until repairs are needed in muscle fibers. Or, they can divide in a different way, so that one cell remains a "stemlike" satellite cell and the other becomes a myoblast and moves into a damaged muscle fiber.
The first process increases the supply of potential repair cells, a supply that's depleted quickly in muscular dystrophy. The second allows the repair work to be done by myoblasts while maintaining adequate numbers of satellite cells if repair demands aren't too great.
Identifying the biochemical steps that underlie these processes should allow scientists to alter the balance between them and ultimately lead to better treatment of muscle degeneration.