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 journalArticle

70 Scopus citations

Abstract

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
Volume23
Issue number2
DOIs
StatePublished - Feb 2009

Keywords

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

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Fingerprint Dive into the research topics of 'Bone marrow-derived cell regulation of skeletal muscle regeneration'. Together they form a unique fingerprint.

  • Cite this

    Sun, D., Martinez, C. O., Ochoa, O., Ruiz-Willhite, L., Bonilla, J. R., Centonze, V. E., Waite, L. L., Michalek, J. E., McManus, L. M., & Shireman, P. K. (2009). Bone marrow-derived cell regulation of skeletal muscle regeneration. FASEB Journal, 23(2), 382-395. https://doi.org/10.1096/fj.07-095901