A role for cell sex in stem cell–mediated skeletal muscle regeneration: female cells have higher muscle regeneration efficiency
Open accessAbstract
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.
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Female muscle-derived stem cells regenerate more efficiently when transplanted into dystrophic mice.
“Specifically, female muscle-derived stem cells regenerate more efficiently when transplanted into dystrophic mice (24).”
From Sex-Based Differences in Skeletal Muscle Kinetics and Fiber-Type Composition (2015) · cites this paper as [24]
Previous studies have identified sex as a determinant for the ability of muscle-derived stem cells to regenerate.
“For instance, previous studies have identified sex as a determinant for the ability of muscle-derived stem cells to regenerate.”
From Sex-Based Differences in Skeletal Muscle Kinetics and Fiber-Type Composition (2015) · cites this paper as [24]
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- Authors
- Deasy, B. M., Lu, A., Tebbets, J. C., Feduska, J. M., Schugar, R. C., Pollett, J. B., Sun, B., Urish, K. L., Gharaibeh, B. M., Cao, B., Rubin, R. T., & Huard, J.
- Affiliations
- Children's Hospital of Pittsburgh (US)
- 5Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles CA 90095
- University of Pittsburgh (US)
- Corresponding author
- Huard, Johnny
- ORCID
- Venue
- The Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2007-04-09
- Volume
- 177
- Issue
- 1
- Pages
- 73-86
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC2064113
- OpenAlex
- W2162184056
- Cited by
- 251
- References
- 56
- Citations by year
- 2026: 4 · 2025: 12 · 2024: 14 · 2023: 9 · 2022: 10 · 2021: 13 · 2020: 24 · 2019: 15 · 2018: 16 · 2017: 8 · 2016: 14 · 2015: 12 · 2014: 10 · 2013: 6 · 2012: 9
- FWCI
- 7.69
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Cell Biology (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- D-Scholarship@Pitt (University of Pittsburgh) (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by-nc-sa)
- Funders
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR049684, R01 AR49684-01)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
- Keywords
- muscle-derived stem cells, skeletal muscle regeneration, dystrophic mice, oxidative stress, hydrogen peroxide, cell differentiation, stem cell heterogeneity
- MeSH terms
- Animals, Cell Differentiation, Female, Male, Regeneration, Sex Factors, Stem Cells, Mice, Inbred mdx, Muscle, Skeletal, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Stem Cell Transplantation, Mice
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