Transplanted neural stem cells promote axonal regeneration through chronically denervated peripheral nerves

摘要: Regeneration in the peripheral nervous system is impaired after prolonged periods of denervation. Currently, no interventions exist to alter outcome To examine role transplanted neural stem cells (NSC), we prepared chronically denervated distal tibial nerve segments. After 6 months chronic denervation, vehicle, C17.2 mouse NSCs, or NSCs engineered overexpress GDNF and performed a peroneal cross-suture. In animals with there was better regeneration axons into as measured by counting number emergence compound motor action potentials innervated foot muscles. Improved correlated reduction chondroitin sulphate proteoglycan (CSPG) immunoreactivity extracellular matrix (ECM). vitro, supernatant from contained large quantities secreted metalloprotease-2 (MMP-2), degraded CSPGs on sections, reversed CSPG-induced inhibition neuritic outgrowth DRG neurons. This reversal inhibited selective MMP-2 inhibitors. first successful demonstration through nerve. These findings suggest that improved PNS can be accomplished combining neurotrophic factor support removal axon growth inhibitory components matrix.