title: A role for cell sex in stem cell-mediated skeletal muscle regeneration: female cells have higher muscle regeneration efficiency.
abstract: 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.
authors.affiliation: Department of Bioengineering, Stem Cell Research Center, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA 15260, USA.
authors.forename: Bridget M
authors.initials: BM
authors.lastname: Deasy
authors.forename: Aiping
authors.initials: A
authors.lastname: Lu
authors.forename: Jessica C
authors.initials: JC
authors.lastname: Tebbets
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Feduska
authors.forename: Rebecca C
authors.initials: RC
authors.lastname: Schugar
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: Pollett
authors.forename: Bin
authors.initials: B
authors.lastname: Sun
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: Urish
authors.forename: Burhan M
authors.initials: BM
authors.lastname: Gharaibeh
authors.forename: Baohong
authors.initials: B
authors.lastname: Cao
authors.forename: Robert T
authors.initials: RT
authors.lastname: Rubin
authors.forename: Johnny
authors.initials: J
authors.lastname: Huard
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D005260:Female; D020869:Gene Expression Profiling; D008297:Male; D051379:Mice; D018101:Mice, Inbred mdx; D018482:Muscle, Skeletal / Q000166:cytology / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D012038:Regeneration / Q000235:genetics / Q000502:physiology*; D012737:Sex Factors; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000145:classification / Q000502:physiology*