March 5, 2009

MDA Scientists Isolate New Type of Muscle Stem Cell

TUCSON, Ariz., March 5, 2009 — A new type of stem cell that may have implications for treating several muscle diseases has been identified by scientists at the University of Colorado at Boulder and at the University of Colorado Health Sciences Center in Aurora, the Muscular Dystrophy Association announced today.

MDA grantee Bradley Olwin at the University of Colorado at Boulder coordinated the scientific team, which also included MDA grantee Dawn Cornelison, now at the University of Missouri at Columbia.

The scientists isolated a rare type of skeletal-muscle stem cell in mice that may be particularly suited to repairing muscles damaged by diseases such as muscular dystrophies.

"The ability to replace lost muscle cells remains an important goal in our arsenal against muscular dystrophies and related diseases," said MDA Senior Vide President Sharon Hesterlee, "We'll be looking at these and other types of muscle stem cells very closely, with an eye toward moving the most effective ones into human testing in the near future."

The newly isolated cells are a subset of previously identified muscle precursors known as muscle SP (side population) cells. SP cells are "stemlike" in their ability to give rise to mature muscle fibers. However, in experiments in mice, relatively few of them engraft into existing muscle tissue after injection.

In their paper published in the journal Cell-Stem Cell, Olwin and colleagues call the newly identified cells "satellite SP cells." They say they believe these cells are the precursors of special muscle-repair cells called satellite cells, which reside near muscle fibers and move in to make repairs as necessary.

In the 1990s, MDA supported several clinical trials in which muscle precursor cells that probably contained mostly satellite cells were taken from close relatives of boys with Duchenne muscular dystrophy (DMD), replicated in laboratories, and injected into the boys' muscles. Unfortunately, the vast majority of the donated cells failed to engraft into the children's muscle fibers. Most of them, experts now believe, were too far along in their maturation to contribute to existing muscle tissue.

Olwin says the satellite SP cells can be distinguished by specific protein markers and have traits that have been ascribed to stem cells in general and muscle stem cells in particular.

When the investigators compared injections of satellite SP cells into mouse muscles with injections of mature satellite cells, they found both types of cells engrafted into muscle fibers. However, the satellite SP cells engrafted in far greater numbers than the mature satellite cells.

Of particular importance, the researchers found that, after 30 days, 75 percent of all satellite cells in the injected mouse muscles were derived from donated satellite SP cells.

When they injected satellite SP cells into leg muscles in mice lacking dystrophin, the protein missing in patients with DMD, they saw extensive muscle regeneration and replenishment of dystrophin.

"These cells are presumably poised to conduct repair operations when needed and can replenish the satellite cells as well as repair muscle," Olwin said. He added that he's encouraged at the large effect of one injection with a small number of cells.

Both Olwin and Cornelison have MDA support to continue working in this area.

About MDA

MDA is the nonprofit health agency dedicated to curing muscular dystrophy, ALS and related diseases by funding worldwide research. The Association also provides comprehensive health care and support services, advocacy and education.