role for cell sex in stem cell-mediated skeletal muscle regeneration: female cells have higher muscle regeneration efficiency

• Published in: The Journal of cell biology 2007-04, Vol.177 (1), p.73-86
• Main Authors: Deasy, Bridget M, Lu, Aiping, Tebbets, Jessica C, Feduska, Joseph M, Schugar, Rebecca C, Pollett, Jonathan B, Sun, Bin, Urish, Kenneth L, Gharaibeh, Burhan M, Cao, Baohong, Rubin, Robert T, Huard, Johnny
• Format: Article
• Language: English
• Subjects: Animals; Cell Differentiation; Cell transplantation; Cellular biology; Cloning; Female; Females; Gene Expression Profiling; Male; Male animals; Mice; Mice, Inbred mdx; Muscle, Skeletal - cytology; Muscle, Skeletal - physiology; Muscles; Muscular dystrophy; Musculoskeletal system; Oligonucleotide Array Sequence Analysis; Oxidative stress; Oxygen; Population mean; Regeneration - genetics; Regeneration - physiology; Rodents; Sex Factors; Skeletal muscle; Skeletal muscle satellite cells; Stem Cell Transplantation; Stem cells; Stem Cells - classification; Stem Cells - physiology; Transplantation
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.200612094

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.