Dyeing to find muscle stem cells.

While the strategy of transplanting muscle cells into people with muscular dystrophies or other muscle diseases makes sense in theory, it has not lived up to its promise. Few transplanted muscle cells survive and form new muscle fibers, notes Louis M. Kunkel of Children's Hospital in Boston. The problem appears to be that most transplanted cells are too set in their ways to regenerate muscle tissues. What's needed, says Kunkel, are muscle stem cells--less specialized cells whose sole purpose is to create new muscle.

At last month's American Society of Gene Therapy meeting in Washington, D.C., Kunkel's coworker Emanuela Gussoni reported progress in finding such stem cells. She, Kunkel, and their colleagues treated muscle tissue with a dye and found a population of cells that took up less of the dye than others did. The researchers borrowed the strategy from Richard Mulligan, also at Children's Hospital, who had accidentally found that a similar difference in dye uptake helps identify blood-forming stem cells in bone marrow.

Hoping that their dye-resistant subpopulation of cells was rich in muscle stem cells, Gussoni and her team injected the cells into female mice having a genetic condition similar to a muscular dystrophy. To prevent rejection of the foreign cells, the researchers irradiated the rodents to destroy their immune systems.

Since the transplanted cells came from male mice, the researchers followed the cells' survival and proliferation by looking for Y chromosomes. After 3 months, around 5 percent of the female rodents' muscle tissue contained cells with a Y chromosome, says Kunkel. The new cells were also making dystrophin, a crucial muscle protein that mice with the dystrophy-like condition are unable to make.

Curiously, bone marrow and spleen tissue also harbored cells with a Y chromosome, indicating that the transplanted cells gave rise to more than muscle. The cellular conversion may go both ways. A report last year showed that bone marrow cells can generate new muscle in addition to blood cells (SN: 3/7/98, p. 150).

Kunkel's team is now trying to determine how muscle stem cells injected into the bloodstream find their way to muscle tissue. For example, the scientists are examining whether exercise that breaks down muscle tissue stimulates the release of a signal that draws stem cells to the area.