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• W2042620000 abstract "Objective(s): Skeletal muscle regeneration requires the presence of macrophages and the expansion of myogenic progenitor cells (MPC), however, the relationship between these diverse cell populations remains an enigma. Monocyte Chemotactic Protein-1, a potent chemokine for macrophage recruitment, acts via a specific receptor, CCR2. We have previously demonstrated severe impairments in muscle regeneration in CCR2 −/− mice. Since CCR2 is expressed on diverse cell types, including MPC, it is possible that ligand binding to CCR2 may promote MPC proliferation and differentiation. Alternatively, recruitment of other cells types, such as macrophages, may alter the local niche to facilitate MPC proliferation and differentiation. In support of the latter, in vitro studies suggest that macrophages increase MPC proliferation, however, in vivo data is lacking. This study evaluated the in vivo relationship between macrophages and MPC after injury as well as the ability of MPC derived from wild type (WT) and CCR2 −/− mice to differentiate in vitro. Methods: Injury was induced following cardiotoxin (CT) injection into hind limb muscles of CCR2 −/− or WT mice (C57Bl/6J background). Flow cytometry was used to estimate tissue neutrophils (PMN, CD11b+/Gr−1+), macrophages (CD11b+/Gr−1−) and MPC (CD34+/Sca−1−/CD45−) at baseline (no injury) or after CT injection. In separate experiments, MPC were isolated from normal muscles of WT and CCR2 −/− mice and cultured in low serum conditions to induce differentiation; MPC proliferation, differentiation and fusion were measured. Results: Tissue macrophage recruitment was delayed and diminished following CT-induced skeletal muscle injury in CCR2 −/− mice compared to WT animals. Macrophage accumulation was maximal within 3 days following injury in WT mice, in contrast, maximal macrophage accumulation in CCR2 −/− animals did not occur until 7 days and was significantly reduced (Fig A). Following injury, MPC were significantly increased in both WT and CCR2 −/− mice by 3 days and achieved a maximum within 7 days, however, MPC were significantly increased in CCR2 −/− animals compared to WT mice at 3, 7, and 14 days after injury (Fig B). Tissue PMN were similar between WT and CCR2 −/− mice except for a significant (p=0.01) increase at day 7 in CCR2 −/− mice. In vitro, the proliferation, differentiation and fusion of CCR2 −/ − and WT MPC were similar." @default.
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• W2042620000 date "2008-02-01" @default.
• W2042620000 modified "2023-09-24" @default.
• W2042620000 title "92. Environmental Factors Determine In Vivo Myogenic Progenitor Cell Function" @default.
• W2042620000 doi "https://doi.org/10.1016/j.jss.2007.12.105" @default.
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