Résumé :
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Macrophages exert either beneficial or deleterious effects on tissue repair, depending on their activation/polarization state. There are crucial for adult skeletal muscle repair, notably by acting on muscle stem cells/myogenic precursors. However, these interactions have not been fully characterized. Here, we explored both in vitro and in vivo in human the interactions of differentially activated MPs with muscle stem cells/precursors during myogenesis and skeletal muscle regeneration. We showed in vitro that through the differential secretion of cytokines and growth factors, pro-inflammatory macrophages inhibited myogenic precursor cell (MPC) fusion while anti-inflammatory macrophages stimulated MPC migration and strongly promoted MPC differentiation by increasing their commitment into differentiated myocytes and the formation of mature myotubes. Furthermore, in vivo time course of expression of myogenic and macrophage markers were studied in regenerating human healthy muscle after damaging. We showed that regenerating areas containing proliferating MPCs were preferentially associated with macrophages expressing pro-inflammatory markers. In the same muscle, regenerating areas containing differentiating myogenin positive MPCs were preferentially coupled to macrophages harboring anti-inflammatory markers. These data demonstrate for the first time in human that macrophages sequentially orchestrate myogenesis during regeneration of damaged skeletal muscle. These results support the emerging concept that inflammation, through macrophage activation, controls stem cell fate and coordinates tissue repair.
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