Ke Xianjin, Li Qian, Xu Li, Zhang Ying, Li Dongmei, Ma Jianhua, Mao Xiaoming
Department of Neurology, Affiliated Hospital of Jiangsu University , Zhenjiang, Jiangsu 212001 , China .
Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University , Nanjing, Jiangsu 210006 , China .
J Biomed Res. 2015 Sep;29(5):380-9. doi: 10.7555/JBR.29.20140076. Epub 2015 Jul 30.
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 1×10(6) 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 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 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 improved the function of the sciatic nerve after injury. This method may be a new treatment of nerve injury.
骨髓间充质干细胞（BMSCs）移植已发展成为一种治疗周围神经系统疾病的新方法。虽然netrin-1是轴突寻路和神经生长的关键分子，但它也可能影响血管网络的形成。在此，我们在大鼠坐骨神经挤压伤模型中研究了移植产生netrin-1的BMSCs的效果。我们造成坐骨神经挤压伤，然后在第二天将1×10(6)个被表达netrin-1的重组腺病毒Ad5-Netrin-1-EGFP感染的BMSCs或培养基注射到损伤部位。在注射后第7天、14天和28天，我们测量运动神经传导，并通过实时PCR检测netrin-1受体UNC5B和结直肠癌缺失基因（DCC）以及神经营养因子脑源性神经营养因子（BDNF）和神经生长因子（NGF）的mRNA表达。我们还通过蛋白质印迹分析检测BDNF和NGF的蛋白表达，并检查整合到髓鞘和血管中的BMSCs。结果显示，被Ad5-Netrin-1-EGFP感染的BMSCs显著改善了坐骨神经的功能，并导致BDNF和NGF表达增加（P<0.05）。此外，损伤后28天，与对照BMSCs相比，在被Ad5-Netrin-1-EGFP感染的BMSCs中发现了更多雪旺细胞。总之，移植产生netrin-1的BMSCs改善了损伤后坐骨神经的功能。该方法可能是一种治疗神经损伤的新方法。
