摘要
Transplantation of bone marrow mesenchymal stem cells （BMSCs） has been developed as a new method of treat- ing 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 1×10^6 BMSCs infected by a recombinant adenovirus expressing netrin-1 Ad5-Netrin-l-EGFP or culture medium into the injured part in the next day. At day 7, 14 and 28 after injection, we measured motor nerve con- duction and detected mRNA expressions of netrin-1 receptors UNC5B 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 AdS-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 AdS- Netrin-l-EGFP compared to control BMSCs. In conclusion, transplantation of BMSCs that produce netrin-1 improved 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 treat- ing 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 1×10^6 BMSCs infected by a recombinant adenovirus expressing netrin-1 Ad5-Netrin-l-EGFP or culture medium into the injured part in the next day. At day 7, 14 and 28 after injection, we measured motor nerve con- duction and detected mRNA expressions of netrin-1 receptors UNC5B 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 AdS-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 AdS- Netrin-l-EGFP compared to control BMSCs. In conclusion, transplantation of BMSCs that produce netrin-1 improved the function of the sciatic nerve after injury. This method may be a new treatment of nerve injury.
基金
supported by grants from Jiangsu Planned Projects for Postdoctoral Research Funds, Nanjing Medical Technology Development Project (No.ZKX08014)
Nanjing Medical Science and Technique Development Foundation,National Natural Science Foundation of China(No.81200594)
