Netrin-1 overexpression in bone marrow mesenchymal stem cells promotes functional recovery in a rat model of peripheral nerve injury

摘要

Transplantation of bone marrow mesenchymal stem cells(BMSCs) has been developed as a new method of treating diseases of the peripheral nervous system.While netrin-1 is a critical molecule for axonal path finding and nerve growth,it may also affect vascular network formation.Here,we investigated the effect of transplanting BMSCs that produce netrin-1 in a rat model of sciatic nerve crush injury.We introduced a sciatic nerve crush injury,and then injected 1X10' BMSCs infected by a recombinant adenovirus expressing netrin-1 Ad5-Netrin-1-EGFP or culture medium into the injured part in the next day.At day 7,14 and 28 after injection,we measured motor nerve conduction and detected mRNA expressions of netrin-1 receptors UNC5 B and Deleted in Colorectal Cancer(DCC),and neurotrophic factors brain-derived neurotrophic factor(BDNF) and nerve growth factor(NGF) by real-time PCR.We also detected protein expressions of BDNF and NGF by Western blotting assays and examined BMSCs that incorporated into myelin and vascellum.The results showed that BMSCs infected by Ad5-Netrin-1-EGFP significantly improved the function of the sciatic nerve,and led to increased expression of BDNF and NGF(P<0.05).Moreover,28 days after injury,more Schwann cells were found in BMSCs infected by Ad5-Netrin-1-EGFP compared to control BMSCs.In conclusion,transplantation of BMSCs that produce netrin-1improved the function of the sciatic nerve after injury.This method may be a new treatment of nerve injury.