Netrin-1 overexpression in bone marrow mesenchymal stem cells promotes functional recovery in a rat

来源 :The Journal of Biomedical Research | 被引量 : 0次 | 上传用户:dl_zsf
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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. Transplantation of bone marrow mesenchymal stem cells (BMSCs) has been developed as a new method of managing diseases of the peripheral nervous system. Whilst neutrinos 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 1 × 10 ’BMSCs infected by a recombinant adenovirus expressing netrin-1 Ad5-Netrin -1-EGFP or culture medium into the injured part in the next day. 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-1 impromptu the function of the sciatic nerve after injury. This method may be a new treatment of nerve injury .
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