Reduced satellite cell population may lead to contractures in children with cerebral palsy

Lucas R. Smith, Henry G. Chambers, Richard L. Lieber*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

71 Scopus citations

Abstract

AIM Satellite cells are the stem cells residing in muscle responsible for skeletal muscle growth and repair. Skeletal muscle in cerebral palsy (CP) has impaired longitudinal growth that results in muscle contractures. We hypothesized that the satellite cell population would be reduced in contractured muscle. METHOD We compared the satellite cell populations in hamstring muscles from participants with CP contracture (n=8; six males, two females; age range 6-15y; Gross Motor Function Classification System [GMFCS] levels II-V; 4 with hemiplegia, 4 with diplegia) and from typically developing participants (n=8; six males, two females, age range 15-18y). Muscle biopsies were extracted from the gracilis and semitendinosus muscles and mononuclear cells were isolated. Cell surface markers were stained with fluorescently conjugated antibodies to label satellite cells (neural cell adhesion molecule) and inflammatory and endothelial cells (CD34 and CD4 respectively). Cells were analyzed using flow cytometry to determine cell populations. RESULTS After gating for intact cells a mean of 12.8% (SD 2.8%) were determined to be satellite cells in typically developing children, but only 5.3% (SD 2.3%; p<0.05) in children with CP. Hemato- poietic and endothelial cell types were equivalent in typically developing children and children with CP (p>0.05) suggesting the isolation procedure was valid. INTERPRETATION A reduced satellite cell population may account for the decreased longitudinal growth of muscles in CP that develop into fixed contractures or the decreased ability to strengthen muscle in CP. This suggests a unique musculoskeletal disease mechanism and provides a potential therapeutic target for debilitating muscle contractures.

Original languageEnglish (US)
Pages (from-to)264-270
Number of pages7
JournalDevelopmental Medicine and Child Neurology
Volume55
Issue number3
DOIs
StatePublished - 2013

Funding

This work was supported by grants from the National Institute of Health (P30AR061303 (high throughput cell sorting core), AR057393 and R24HD050837), the Department of Veterans Affairs and the Department of Defense through the National Defense Science and Engineering Graduate Fellowship Program. We acknowledge Drs. Eric Edmonds and Andrew Pennock for assistance collecting biopsies, Dr. Alessandra Sacco and Dr. Gretchen Meyer for assistance developing the flow cytometry techniques, and Shannon Bremner for technical assistance.We also acknowledge the use of the flow cytometry core at the Sanford-Burnham Institute and the expertise of Drs. Yoav Altman and Amy Cortez. This work was supported by grants from the National Institute of Health (P30AR061303 (high throughput cell sorting core), AR057393 and R24HD050837), the Department of Veterans Affairs and the Department of Defense through the National Defense Science and Engineering Graduate Fellowship Program. We acknowledge Drs. Eric Edmonds and Andrew Pennock for assistance collecting biopsies, Dr. Alessandra Sacco and Dr. Gretchen Meyer for assistance developing the flow cytometry techniques, and Shannon Bremner for technical assistance. We also acknowledge the use of the flow cytometry core at the Sanford-Burnham Institute and the expertise of Drs. Yoav Altman and Amy Cortez.

ASJC Scopus subject areas

  • Clinical Neurology
  • Developmental Neuroscience
  • Pediatrics, Perinatology, and Child Health

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