Coupling between Myogenesis and Angiogenesis during Skeletal Muscle Regeneration Is Stimulated by Restorative Macrophages

Stem Cell Reports. 2017 Dec 12;9(6):2018-2033. doi: 10.1016/j.stemcr.2017.10.027. Epub 2017 Nov 30.


In skeletal muscle, new functions for vessels have recently emerged beyond oxygen and nutrient supply, through the interactions that vascular cells establish with muscle stem cells. Here, we demonstrate in human and mouse that endothelial cells (ECs) and myogenic progenitor cells (MPCs) interacted together to couple myogenesis and angiogenesis in vitro and in vivo during skeletal muscle regeneration. Kinetics of gene expression of ECs and MPCs sorted at different time points of regeneration identified three effectors secreted by both ECs and MPCs. Apelin, Oncostatin M, and Periostin were shown to control myogenesis/angiogenesis coupling in vitro and to be required for myogenesis and vessel formation during muscle regeneration in vivo. Furthermore, restorative macrophages, which have been previously shown to support myogenesis in vivo, were shown in a 3D triculture model to stimulate myogenesis/angiogenesis coupling, notably through Oncostatin M production. Our data demonstrate that restorative macrophages orchestrate muscle regeneration by controlling myogenesis/angiogenesis coupling.

Keywords: angiogenesis; macrophages; muscle stem cells; myogenesis; skeletal muscle regeneration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apelin / genetics
  • Blood Vessels / growth & development
  • Blood Vessels / metabolism
  • Cell Adhesion Molecules / genetics
  • Cell Differentiation / genetics*
  • Cell Movement / genetics
  • Endothelial Progenitor Cells / metabolism
  • Gene Expression Regulation, Developmental / genetics
  • Humans
  • Macrophages / metabolism
  • Mice
  • Muscle Development / genetics*
  • Muscle, Skeletal / growth & development*
  • Myoblasts / cytology
  • Myoblasts / metabolism
  • Neovascularization, Physiologic / genetics*
  • Oncostatin M / genetics
  • Regeneration / genetics*
  • Stem Cells / cytology
  • Stem Cells / metabolism
  • Wound Healing


  • Apelin
  • Cell Adhesion Molecules
  • POSTN protein, human
  • Oncostatin M