Contribution of minced muscle graft progenitor cells to muscle fiber formation after volumetric muscle loss injury in wild-type and immune deficient mice

Volumetric muscle injury (VML) causes an irrecoverable loss of muscle fibers, persistent strength deficits, and chronic disability. A crucial challenge to VML injury and possible regeneration is the removal of all of the in situ native elements necessary for skeletal muscle regeneration. Our first goal was to establish a reliable VML model in the mouse tibialis anterior (TA) muscle. In adult male wild-type and nude mice, a non-repaired ≈20% VML injury to the TA muscle resulted in an ≈59% loss in nerve evoked muscle strength, ≈33% loss in muscle mass, and ≈29% loss of muscle fibers at 28 day post-injury. Our second goal was to investigate if minced muscle grafts (≈1 mm³ tissue fragments) promote recovery of muscle fibers after VML injury and to understand if the graft-derived progenitor cells directly contribute to fiber regeneration. To assess donor cell contribution, donor muscle tissue was derived from UBC-GFP mice in a subset of experiments. Minced grafts restored ≈34% of the lost fibers 28 days post-injury. The number of GFP⁺ fibers and the estimated number of regenerated fibers were similar, regardless of host mouse strain. The muscle tissue regeneration promoted by minced grafts did not improve TA muscle strength at this time post-injury. These findings demonstrate the direct contribution of minced muscle graft-derived myogenic stem/progenitor cells to recovery of muscle fibers after VML injury and signify the utility of autologous myogenic stem cell therapies for this indication.