兔脊髓损伤不同时期的神经干细胞移植治疗的效果

Therapeutic effect of neural stem cell transplantation at different time points after rabbit spinal cord injury

目的:研究新西兰大白兔脊髓损伤后不同时期神经干细胞(neuralstemcells,NSCS)移植治疗的不同效果,探讨脊髓损伤移植治疗的最佳时机。方法:体外培养、诱导新西兰大白兔骨髓基质细胞(bonemarrowstromalcells,BMSCs)为NSC并行5-溴-2-脱氧尿苷(bromodeoxyuridine/5-bromo-2-deoxyuridine,BrdU)标记。手术造成兔脊髓全横断模型,在术后即时,7,14,21,28d分别行NSC局部移植,同时设立脊髓全横断空白对照组,正常对照组。于移植后3个月观察动物脊髓损伤局部病理变化。结果:术后即时移植组局部仅有少量Brdu标记阳性细胞存活,通过脊髓损伤区的神经纤维数目少;7,14d移植组局部有大量Brdu标记阳性细胞存活,通过脊髓损伤区的神经纤维数目多,神经纤维排列较整齐;21,28d移植组局部有大量Brdu标记阳性细胞存活,但通过脊髓损伤区的神经纤维数目少,且再生的神经纤维排列紊乱;空白对照组未发现Brdu标记阳性细胞,在脊髓损伤区域未发现再生通过的神经纤维。结论:实验证明了脊髓损伤后7～14d为NSC最佳移植时期,同时提示NSC移植对动物脊髓损伤后的组织修复具有促进作用。

AIM:To investigate the therapeutic effect of neural stem cell (NSC) transplantation at different time after the spinal cord injury in rabbits, and to explore the optimal time point of NSC transplantation. METHODS:NSCs were induced from bone marrow stromal cells (BMSCs), and then marked with 5 bromo 2 deoxy uridine (Brdu).The NSC transplantation was performed in different periods after model operation of spinal cord transection, including 0 hour, 7th, 14th, 21st and 28th day following the operation. There were two control groups, one of which did not receive the NSC transplantation after the model operation, and another one was normal without any operation or transplantation. The slices of spinal cord were studied 3 months after NSC transplantation. RESULTS:Only a few BrdU positive cells survived immediately after the model operation,and nerve fibers seldom passed through the injury area, too. In 7th and 14th day groups, plenty of BrdU positive cells presented, and much more nerve fibers passed through the injury area in well arranged. In 21st and 28th day groups, there were also plenty of BrdU positive cells to survive well, but still only a few nerve fibers passed through the injured area, and arranged irregularly. In normal control group, neither BrdU positive cells were found, nor nerve fiber passed through the injured area. CONCLUSION:The 7th to 14th days after injury model operation are the best period to transplant neural stem cells into the injured spinal cord of the model rabbits.