Severe nerve damage is often irreparable and can lead to reduced muscle function, impaired sensation, and painful neuropathy. Stem cells isolated from adult muscle tissue can give rise to cells with neuronal phenotypes in vitro, and recently muscle-derived stem/progenitor cells (MDSPCs) have been shown to have the capacity to regenerate several types of tissue in murine models. Mitra Lavasani and colleagues demonstrated that human-derived MDSPCs (hMDSPCs) can be induced to adopt neuronal and glial characteristics in vitro. Engraftment of hMDSPCs into an area of severe nerve injury in a murine model promoted axonal regeneration, dramatically improved function, and reduced muscle atrophy. Furthermore, mice that received hMDSPC transplants did not exhibit any adverse side effects. Together, these data indicate that hMDSPC transplantation should be further explored for its clinical potential to regenerate nervous tissue. The accompanying image shows toluidine blue stained sections from a regenerated nerve at 12 weeks post hMDSPC transplantation, revealing nerve fibers with organized fascicles surrounded with perineurium.
Peripheral nerve injuries and neuropathies lead to profound functional deficits. Here, we have demonstrated that muscle-derived stem/progenitor cells (MDSPCs) isolated from adult human skeletal muscle (hMDSPCs) can adopt neuronal and glial phenotypes in vitro and ameliorate a critical-sized sciatic nerve injury and its associated defects in a murine model. Transplanted hMDSPCs surrounded the axonal growth cone, while hMDSPCs infiltrating the regenerating nerve differentiated into myelinating Schwann cells. Engraftment of hMDSPCs into the area of the damaged nerve promoted axonal regeneration, which led to functional recovery as measured by sustained gait improvement. Furthermore, no adverse effects were observed in these animals up to 18 months after transplantation. Following hMDSPC therapy, gastrocnemius muscles from mice exhibited substantially less muscle atrophy, an increase in muscle mass after denervation, and reorganization of motor endplates at the postsynaptic sites compared with those from PBS-treated mice. Evaluation of nerve defects in animals transplanted with vehicle-only or myoblast-like cells did not reveal histological or functional recovery. These data demonstrate the efficacy of hMDSPC-based therapy for peripheral nerve injury and suggest that hMDSPC transplantation has potential to be translated for use in human neuropathies.
Mitra Lavasani, Seth D. Thompson, Jonathan B. Pollett, Arvydas Usas, Aiping Lu, Donna B. Stolz, Katherine A. Clark, Bin Sun, Bruno Péault, Johnny Huard