Neuronal Regeneration in Sciatic Nerve Injury Mouse Model Following Treatment with Human Muscle Progenitor Cells Overexpressing Neurotrophic Factors

The peripheral nervous system has an intrinsic ability to regenerate after injury. However, this process is slow, incomplete, and often accompanied by disturbing motor and sensory consequences. The main goal of this study is to examine the feasibility of administration of human muscle progenitor cells (hMPC) overexpressing neurotrophic factor (NTF) genes, known to protect peripheral neurons and enhance axon regeneration and functional recovery, to ameliorate motoric and sensory deficits in sciatic nerve injury (SNI) mouse model, which is the most common model for studying peripheral nerve injury.

To this end, hMPC were isolated from a human muscle biopsy, and manipulated to ectopically express BDNF, GDNF, VEGF, and IGF-1. ELISA analysis verified that the genetically manipulated cells express significant amounts of these NTF. Transplantation of the hMPC-NTF was shown to improve motor function and gait pattern in mice following SNI surgery, as indicated by the CatWalk XT system. Moreover, using the hot-plate test, the treated mice showed less sensory deficits, indicating a palliative effect of the treatment. ELISA analysis following transplantation demonstrated increased NTF expression levels in the gastrocnemius muscle of the treated mice, reinforcing the hypothesis that the observed positive effect was due to the transplantation of the genetically manipulated cells.

The use of hMPC-NTF demonstrates the feasibility of a treatment paradigm, which may lead to rapid, high-quality healing of damaged peripheral nerves due to administration of hMPC. Our approach suggests a possible clinical application for the treatment of peripheral nerve injury.