Spotlight on Research 2007

December 2007 (historical)

Sex of Adult Mouse Muscle Stem Cells Affects Their Muscle Regeneration Efficiency

Researchers have recently discovered that the sex of cells in a subpopulation of muscle-generating stem cells in adult mice can considerably influence their capacity to repair tissue. The finding may persuade researchers to consider the implication of relying on only male cells or female cells in research, and to report the sex of the stem cells used when publishing their findings. Their work was partly supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS).

The research was carried out by Johnny Huard, Ph.D., and his colleagues at the University of Pittsburgh , and reported in the Journal of Cell Biology . The scientists were studying the capability of self-renewal in muscle-derived stem cells (MDSCs). MDSCs are a subpopulation of adult muscle stem cells obtained from skeletal muscles of normal mice. The researchers found that female MDSCs participated in skeletal muscle regeneration more efficiently than their male counterparts, as shown after being transplanted into the muscles of "mdx mice," an animal model of one type of muscular dystrophy.

The research team then tried to find out the causes of this fascinating difference in regenerative capacity between cell sexes. They showed that in culture dishes, male and female MDSCs seem to behave differently when exposed to a low oxygen environment. In this stressful situation, the male cells converted more readily to mature muscle fibers. The scientists postulate that male MDSCs differentiate faster than female MDSCs after transplantation into mdx mice, so that soon the original male stem cells are almost used up. With the resulting lack of stem cells, few muscle cells could be further generated. This might explain why eventually female MDSCs can give rise to more muscle cells than their male counterparts after being transplanted into the muscles of mdx mice.

Dr. Huard and his colleagues suggested that more research needs to be done in other types of stem cells to see if they demonstrate similar differences due to cell sex. Another issue of importance is the need for researchers to determine and report the influence of cell sex on the results of their research using stem cells.

Several types of adult stem cells are currently being studied to see if they are capable of regenerating skeletal muscles. Scientists are hoping that in the future stem cells could be used to help regenerate wasted muscle in patients with muscular dystrophy, a collection of genetic disorders in which muscle cells become progressively more damaged and die. Although enormous progress has been made in elucidating the molecular basis of some dystrophies, there is currently no effective therapy for them. Several different approaches are being studied for treating muscular dystrophy, including gene therapy, pharmacological therapy and cell therapy.

Other support for this research came from the Jesse's Journey Foundation, the Muscular Dystrophy Association, Children's Hospital of Pittsburgh , and the University of Pittsburgh .

The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the Department of Health and Human Services' National Institutes of Health, is to support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases; the training of basic and clinical scientists to carry out this research; and the dissemination of information on research progress in these diseases. For more information about NIAMS, call the information clearinghouse at (301) 495-4484 or (877) 22-NIAMS (free call) or visit the NIAMS Web site at http://www.niams.nih.gov .

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Deasy BM, et al. A role for cell sex in stem cell-mediated skeletal muscle regeneration: female cells have higher muscle regeneration efficiency. Journal of Cell Biology 2007;177(1):73-86.