The development of immunomodulatory approaches to restore skeletal muscle function after injury



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Efficient restoration of skeletal muscle function after severe injury is a major goal of intervention therapies. Ischemia/reperfusion (I/R) injury to skeletal muscle leads to exaggerated inflammatory response and significant ultrastructural tissue damage slowing restoration of muscular structure and function. Herein, we used animal model of tourniquet-induced ischemia/reperfusion injury (TK-I/R) to test the effects of exogenously delivered growth factors and cells on skeletal muscle regeneration. The delivery of PEGylated fibrin along with stromal cell derived factor-1α and/or insulin-like growth factor-I into acutely injured muscle, differentially affected functional muscle regeneration. These data suggest that local balance and release kinetics of growth factors in the tissue microenvironment can significantly impact the success of skeletal muscle repair. Cell-mediated treatment of I/R-injured muscle demonstrated significant tissue regeneration using adoptively transferred and in vitro polarized macrophages. Functional activation status of transplanted macrophage populations impacted the outcome of muscle repair. We showed that increasing macrophage populations at the site of injury in temporally regulated manner is beneficial for efficient recovery of muscle force and function.