Female stem cells flourish: sex difference could affect therapies.

When it comes to stem cells, sex matters. Muscle stem cells taken from female mice repair damaged tissues better than male stem cells do, according to a new study.

It's the first demonstration that the regenerative abilities of stem cells depend on their sex. Currently, researchers don't typically document whether the cell lines that they study came from males or females.

"[Scientists] could have biased results if they're only looking at one gender of the cells," says Bridget M. Deasy of the University of Pittsburgh.

She and her colleagues began looking into the role of gender in stem cell performance after they realized that the cell lines that they had been using for years, which they had chosen because those cells regenerated well, were all female. "We really were unaware of it," she says.

To isolate the influence of the cells' sex, Deasy and her colleagues cultivated stem cell lines derived from the healthy muscle tissue of 15 female and 10 male mice. Unlike more-controversial embryonic stem cells, muscle stem cells come from adult animals' tissues and can be extracted without killing the animal.

The researchers implanted the muscle stem cells into mice that had a condition similar to human muscular dystrophy. Two weeks later, the team counted the healthy muscle fibers generated by the stem cells. Only one of the male cell lines produced more than 200 new fibers, while six of the female lines did, the researchers report in the April 9 Journal of Cell Biology.

"It is a new idea in stem cell research," comments Barbara D. Boyan of the Georgia Institute of Technology in Atlanta, who examines sex differences in mature body cells. It makes sense that the sex of stem cells should matter, she says.

Deasy says, "It should come down to some kind of difference in the X and Y chromosomes, but the truth is that we just don't know yet." The exact mechanism behind the difference could take years to decipher, she adds.

In the recent work, Deasy's group found that certain stress-response genes were more active in the implanted female cells than in the male cells. Transplantation stresses cells, so the researchers suggest that sex differences in stress response might explain the performance gap.

Understanding the mechanism behind the male-female difference might be useful if doctors eventually transplant stem cells in therapies to repair damaged tissues, as many scientists expect. For example, researchers might find a way to impart the female trait to male stem cells, thereby improving the success of future therapies that would alter and then reimplant a man's own stem cells.