Evaluation of bone marrow mononuclear cells as an adjunct therapy to minced muscle graft for the treatment of volumetric muscle loss injuries

Abstract

BackgroundThe delivery of alternative myogenic cell sources to enhance the efficacy of minced muscle grafts (MG) for the treatment of volumetric muscle loss (VML) injuries is a promising strategy to overcome the demand on muscle-derived donor tissue that currently limits the translation of this therapy.MethodsUsing a rat model of VML, bone marrow mononuclear cells (BMNCs) were evaluated for their ability to directly contribute to de novo muscle fiber regeneration by transplanting MG in a collagen carrier at a dose of 50% of the VML injury both with and without concomitant delivery of 5 million BMNCs derived via density gradient centrifugation from the bone marrow of a syngeneic green fluorescent protein (GFP)+ donor.ResultsHistological, molecular, and functional analyses revealed that BMNCs can engraft with co-delivered MG and contribute to nascent myofiber, but do so at a low magnitude without resulting in significant changes to transcription of key myogenic genes or gains in whole muscle force generation relative to MG alone.ConclusionAs such, co-delivery of BMNCs with MG is a promising treatment paradigm to VML that will require further investigation to identify the phenotype and therapeutic dosing of the bone marrow-derived cell populations which engraft most efficiently.