Cited by 474Muscle Physiology and DisordersNeurogenetic and Muscular Disorders ResearchPluripotent Stem Cells Research

Highly Efficient, Functional Engraftment of Skeletal Muscle Stem Cells in Dystrophic Muscles

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Cerletti, Massimiliano, Jurga, Sara, Witczak, Carol A., Hirshman, Michael F., Shadrach, Jennifer L., Goodyear, Laurie J., Wagers, Amy J.·2008·Cell

Abstract

Satellite cells reside beneath the basal lamina of skeletal muscle fibers and include cells that act as precursors for muscle growth and repair. Although they share a common anatomical localization and typically are considered a homogeneous population, satellite cells actually exhibit substantial heterogeneity. We used cell-surface marker expression to purify from the satellite cell pool a distinct population of skeletal muscle precursors (SMPs) that function as muscle stem cells. When engrafted into muscle of dystrophin-deficient mdx mice, purified SMPs contributed to up to 94% of myofibers, restoring dystrophin expression and significantly improving muscle histology and contractile function. Transplanted SMPs also entered the satellite cell compartment, renewing the endogenous stem cell pool and participating in subsequent rounds of injury repair. Together, these studies indicate the presence in adult skeletal muscle of prospectively isolatable muscle-forming stem cells and directly demonstrate the efficacy of myogenic stem cell transplant for treating muscle degenerative disease.

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Crossref · 10.1016/j.cell.2008.05.049

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  • Dedicated muscle stem cells, also called satellite cells, support repair of skeletal muscle.

    “Skeletal muscle repair is facilitated by a population of dedicated muscle stem cells (MuSCs), also known as satellite cells, that reside in anatomically defined niches within muscle tissues.”
  • Multiple rounds of self-renewing divisions by MuSCs are required for their regenerative function, as shown by transplantation, genetic ablation, and lineage tracing.

    “Subsequently, MuSCs undergo multiple rounds of self-renewing divisions that are essential to their function in regeneration, as demonstrated by transplantation, genetic ablation, and lineage tracing experiments5–12.”
  • Multiple groups have reported that transplanting satellite cells into dystrophic or injured/irradiated mouse muscle can refill the stem cell pool.

    “Several groups have reported successful replenishment of the stem cell pool by satellite cell transplantation into dystrophic or irradiated/injured muscles in mice120,139,140, although the rarity of satellite cells in muscle tissue has been a challenge for translating muscle stem cell transplantation to clinical practice141”

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Authors
Cerletti, M., Jurga, S., Witczak, C. A., Hirshman, M. F., Shadrach, J. L., Goodyear, L. J., & Wagers, A. J.
Affiliations
Joslin Diabetes Center (US)
Corresponding author
Wagers, Amy J.
Venue
Cell
Publisher
Elsevier BV
Published
2008-07
Volume
134
Issue
1
Pages
37-47
ISSN
0092-8674 (ISSN-L)
OpenAlex
W2019428638
Cited by
472
References
49
Citations by year
2026: 4 · 2025: 5 · 2024: 16 · 2023: 14 · 2022: 9 · 2021: 24 · 2020: 31 · 2019: 23 · 2018: 19 · 2017: 18 · 2016: 29 · 2015: 29 · 2014: 33 · 2013: 39 · 2012: 46
FWCI
18.26
Type
journal article
Language
en
Open access
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • UCL Discovery (University College London) (submittedVersion)
Funders
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK068626)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (F32AR051663)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
  • Health Sciences › Medicine › Genetics › Neurogenetic and Muscular Disorders Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
Keywords
skeletal muscle stem cells, satellite cells, dystrophic muscle, mdx mice, dystrophin deficiency, cell transplantation, muscle regeneration, stem cell heterogeneity, stem cell engraftment
MeSH terms
Animals, Cell Separation, Humans, Membrane Proteins, Mice, Inbred C57BL, Muscle Contraction, Muscular Dystrophy, Animal, Dystrophin, Muscle, Skeletal, Satellite Cells, Skeletal Muscle, Stem Cell Transplantation, Mice, Adult Stem Cells

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