Résumé :
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Skeletal muscle regeneration relies onto a specific population of myogenic precursors, named satellite cells. Inflammation also has a determinant role, as upon injuring macrophages are attracted by the damaged myofibers and the activated satellite cells and act as key elements of dynamic muscle supportive stroma. Yet, it is not kwown how macrophages interact with the more profound stem cells of the satellite cell niche. In this study we show that in the presence of a murine macrophage conditioned medium (mMCM) a subpopulation of stem-like cells could be selected and expanded from adult rat muscle with serial platings. These cells were small, round, poorly adhesive, slow-growing and showed mesenchimal differentiation plasticity. mMCM also inhibited the mesenchimal potential towards adipogenesis of satellite cells mechanically isolated from suspensions of single myofibers. mMCM-treated myogenic cells in mixed primary muscle cultures from neonatal rats showed a growth rate increase, spindle-like morphology and alignment before forming an impressive array of contracting myotubes; comparison with cultures from adult muscles suggested that mMCM-sensitive cells are more abundant in developing muscles. In vivo, intramuscolar administrations of concentrated mMCM in a model of extensive surgical ablation of rat tibialis anterior dramatically improved muscle regeneration. Altogether, these findings suggest that macrophagic factors could be of great help in developing therapeutic protocols with myogenic stem cells.
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