Myoblast Therapy Ameliorates Skeletal Muscle Atrophy Resulting From Chronic Denervation

INTRODUCTION/AIMS: Skeletal muscle undergoes progressive denervation-induced muscle atrophy (DIMA) after peripheral nerve injury that severely impairs the potential for motor functional recovery with reinnervation. There are currently no therapeutic strategies to reverse the deleterious effects of chronic DIMA, leaving affected patients with lifelong disability. Herein, we used a translational rodent forelimb nerve injury model to investigate whether targeted injection of syngeneic myoblasts to chronically atrophic muscle can reverse the histologic and functional consequences of DIMA. METHODS: Male Lewis rats underwent median nerve transection followed by immediate (positive control) or delayed repair. Following a plateau of motor function, myoblasts were injected into the digital flexor muscles (n = 5-6 per group), delivered in either saline or a nanofiber hydrogel composite (NHC) loaded with agrin- and insulin-like growth factor 1 (IGF-1)-releasing nanoparticles (npNHC). Serial functional assessments of stimulated grip strength and terminal histological evaluation were used to measure recovery. RESULTS: ) myoblast therapy caused sustained improvement in stimulated grip strength from pretreatment baseline (p < 0.05). Histological evaluation demonstrated that myoblast therapy, when delivered in npNHC, reversed whole muscle atrophy compared to positive controls [p = 0.997 and 0.996] and restored mean myofiber cross-sectional area [p = 0.244]. Correlation analysis demonstrated functional improvements were associated with increased myofiber cross-sectional area [r = 0.900, p = 3.01E-09]. DISCUSSION: This data indicates that targeted injection of syngeneic myoblasts can reverse the functional and histologic effects of DIMA in skeletal muscles and is a promising strategy for improving recovery after peripheral nerve injuries.