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Published online April 9, 2007
doi:10.1083/jcb.200612094
The Journal of Cell Biology, Vol. 177, No. 1, 73-86
The Rockefeller University Press, 0021-9525 $30.00
© 2007 Deasy et al.
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 A role for cell sex in stem cell–mediated skeletal muscle regeneration: female cells have higher muscle regeneration efficiency

Bridget M. Deasy1,2,3, Aiping Lu3, Jessica C. Tebbets3, Joseph M. Feduska3, Rebecca C. Schugar3, Jonathan B. Pollett2,3, Bin Sun3, Kenneth L. Urish1,3, Burhan M. Gharaibeh2,3, Baohong Cao2,3, Robert T. Rubin5, and Johnny Huard1,2,3,4

1 Department of Bioengineering, 2 Department of Orthopaedic Surgery, 3 Stem Cell Research Center, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, and 4 Department of Molecular Genetics and Biochemistry, University of Pittsburgh, Pittsburgh, PA 15260
5 Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles CA 90095

Correspondence to Johnny Huard: jhuard{at}pitt.edu

We have shown that muscle-derived stem cells (MDSCs) transplanted into dystrophic (mdx) mice efficiently regenerate skeletal muscle. However, MDSC populations exhibit heterogeneity in marker profiles and variability in regeneration abilities. We show here that cell sex is a variable that considerably influences MDSCs' regeneration abilities. We found that the female MDSCs (F-MDSCs) regenerated skeletal muscle more efficiently. Despite using additional isolation techniques and cell cloning, we could not obtain a male subfraction with a regeneration capacity similar to that of their female counterparts. Rather than being directly hormonal or caused by host immune response, this difference in MDSCs' regeneration potential may arise from innate sex-related differences in the cells' stress responses. In comparison with F-MDSCs, male MDSCs have increased differentiation after exposure to oxidative stress induced by hydrogen peroxide, which may lead to in vivo donor cell depletion, and a proliferative advantage for F-MDSCs that eventually increases muscle regeneration. These findings should persuade researchers to report cell sex, which is a largely unexplored variable, and consider the implications of relying on cells of one sex.

Abbreviations used in this paper: ANOVA, analysis of variance; F-MDSC, female MDSC; GM, growth medium; MDSC, muscle-derived stem cell; M-MDSC, male MDSC; MyHC, myosin heavy chain; PD, population doubling; PDT, PD time; RI, regeneration index; ROS, reactive oxygen species; SCID, severe combined immunodeficiency.


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