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

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 considerabl...

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Bibliographic Details
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
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Summary: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.
ISSN:0021-9525
1540-8140
DOI:10.1083/jcb.200612094