Bone marrow-derived cell regulation of skeletal muscle regeneration

Dongxu Sun, Carlo O. Martinez, Oscar Ochoa, Lourdes Ruiz-Willhite, Jose R. Bonilla, Victoria E. Centonze, Lindsay L. Waite, Joel E. Michalek, Linda M. McManus, Paula K. Shireman

Research output: Contribution to journalArticlepeer-review

81 Scopus citations


Limb regeneration requires the coordination of multiple stem cell populations to recapitulate the process of tissue formation. Therefore, bone marrow (BM) -derived cell regulation of skeletal muscle regeneration was examined in mice lacking the CC chemokine receptor 2 (CCR2). Myofiber size, numbers of myogenic progenitor cells (MPCs), and recruitment of BM-derived cells and macrophages were assessed after cardiotoxin-induced injury of chimeric mice produced by transplanting BM from wild-type (WT) or CCR2-/- mice into irradiated WT or CCR2-/- host mice. Regardless of the host genotype, muscle regeneration and recruitment of BM-derived cells and macrophages were similar in mice replenished with WT BM, whereas BM-derived cells and macrophage accumulation were decreased and muscle regeneration was impaired in all animals receiving CCR2-/- BM. Furthermore, numbers of MPCs (CD34+/Sca-1-/CD45- cells) were significantly increased in mice receiving CCR2-/- BM despite the decreased size of regenerated myofibers. Thus, the expression of CCR2 on BM-derived cells regulated macrophage recruitment into injured muscle, numbers of MPC, and the extent of regenerated myofiber size, all of which were independent of CCR2 expression on host-derived cells. Future studies in regenerative medicine must include consideration of the role of BM-derived cells, possibly macrophages, in CCR2-dependent events that regulate effective skeletal muscle regeneration.

Original languageEnglish (US)
Pages (from-to)382-395
Number of pages14
JournalFASEB Journal
Issue number2
StatePublished - Feb 2009


  • CC chemokine receptor 2
  • CCR2
  • Chimera
  • Inflammation
  • Monocyte/macrophage
  • Myogenic progenitor cell

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics


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