The effects of human muscle derived stem cells on the induction of peripheral nerve regeneration

Purpose: In this study, we evaluated the extent of functional and histological axonal regeneration after resection of the sciatic nerve. The nerve was repaired with silicone tubes filled with human muscle derived stem cells (MDSCs) and neuronal progenitor cells (NPCs) in nude mice. Materials and Methods: The human muscle samples were obtained from the rectus abdominis muscle of 12 patients that underwent a laparotomy. The MDSCs were isolated using a modified preplate technique. Using the MDSCs, neurogenic differentiation was induced by dissociating neurospheres produced in a neurosphere culture medium containing neuronal induction agents. A part of the sciatic nerve, approximately 7 mm in length, was excised bilaterally, and a 9mm long silicone tube guide was placed at the resulting gap in 40 nude mice. The transplanted sites were divided randomly into three groups according to the type of grafting cells: silicone tube guides filled with PBS (P group, n=20), silicone tube guides filled with MDSCs (M group, n=40) and silicone tube guides filled with NPCs (N group, n=20). Histological observations and a nerve conduction study were performed 12 weeks after the graft. Results: The number and diameter of the myelinated axons were significantly increased in the M and N groups (p<0.001). In a nerve conduction study, the amplitude of the compound muscle action potential (CMAP) and motor latency of response were significantly higher and shorter in the M and N groups (p<0.001). Moreover, reaction with neuronal class III β-tubulin (Tuj1, a neuronal marker) and antiglial fibrillary acidic protein (GFAP, a ghal marker) was observed in the regenerated nerve that originated from the M and N groups. Conclusions: These results show that MDSCs can differentiate into NPCs and improve the peripheral nerve regeneration rate after transplantation into a nerve guide.