Muscle-derived stem/progenitor cell dysfunction in Zmpste24-deficient progeroid mice limits muscle regeneration

Minjung Song, Mitra Lavasani, Seth D. Thompson, Aiping Lu, Bahar Ahani, Johnny Huard*

*Corresponding author for this work

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Introduction. Loss of adult stem cell function during aging contributes to impaired tissue regeneration. Here, we tested the aging-related decline in regeneration potential of adult stem cells residing in the skeletal muscle. Methods. We isolated muscle-derived stem/progenitor cells (MDSPCs) from progeroid Zmpste24-deficient mice (Zmpste24§ssup§-/-§esup§) with accelerated aging phenotypes to investigate whether mutation in lamin A has an adverse effect on muscle stem/progenitor cell function. Results: Our results indicate that MDSPCs isolated from Zmpste24§ssup§-/- §esup§mice show reduced proliferation and myogenic differentiation. In addition, Zmpste24§ssup§-/- §esup§MDSPCs showed impaired muscle regeneration, with a limited engraftment potential when transplanted into dystrophic muscle, compared with wild-type (WT) MDSPCs. Exposure of progeroid Zmpste24§ssup§-/- §esup§MDSPCs to WT MDSPCs rescued the myogenic differentiation defect in vitro. Conclusions: These results demonstrate that adult stem/progenitor cell dysfunction contributes to impairment of tissue regeneration and suggest that factors secreted by functional cells are indeed important for the therapeutic effect of adult stem cells.

Original languageEnglish (US)
Article number33
JournalStem Cell Research and Therapy
Volume4
Issue number2
DOIs
StatePublished - 2013

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Cell Biology

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