Female Mice Stem Cells
Lead to More Regeneration

Stem cells taken from the muscles of healthy mice and transplanted into the muscles of mice with a disease resembling Duchenne muscular dystrophy (DMD) are more effective at causing muscle regeneration if they’re taken from female, rather than male, donors, say MDA-supported investigators at Children’s Hospital of Pittsburgh, the University of Pittsburgh and the University of California-Los Angeles.

Researchers in the laboratory of Johnny Huard at the University of Pittsburgh, who published their findings in the April 9 issue of the Journal of Cell Biology, say they think the difference may be caused by “innate sex-related differences in the cells’ stress responses.”

Their experiments, they say, show that the superior regenerative abilities of the female-derived stem cells is probably not directly related to hormonal factors or to a difference in the immune response to male versus female cells.

Instead, they say, it seems to be related to the female-derived stem cells’ propensity for staying immature and proliferating for the first three days or so after transplantation, while the male-derived cells tend to mature (differentiate) immediately into muscle cells.

After three days, they say, the environment in which the new cells find themselves becomes more hospitable, with less inflammation and more oxygen available. The female cells, many of which will have survived and proliferated during the early phase of transplantation, can then differentiate, fusing with muscle fibers and causing them to regenerate.

But many of the male cells will by this time have already matured in the more hostile circumstances and been killed by cellular defenses, leading to the regeneration of a smaller number of muscle fibers.

The investigators say it will be interesting to see whether other stem cell types exhibit sex-related differences, as well as to determine the extent to which these may account for varying experimental results.

Their new findings, Huard said, “may shed light on the conflicting results in the literature on stem cells, since in many instances the gender of the animals and the donor are not even characterized.”