人脂肪间充质干细胞静脉移植修复脊髓损伤:相关因子及行为学评价

Intravenous transplantation of human adipose-derived mesenchymal stem cells for the treatment of spinal cord injury:Correlation factor and behavior evaluation

背景:研究证实脂肪间充质干细胞在体外经丹参等诱导剂诱导后可分化为神经元样细胞,因此有可能成为治疗脊髓损伤新的种子细胞。目的:探讨脂肪间充质干细胞尾静脉移植后,对急性闭合性脊髓损伤大鼠行为学及损伤脊髓组织中各因子表达的影响。方法:无菌条件下体外分离培养人脂肪间充质干细胞,传至第4代,将细胞收集并制成浓度为1×109L-1细胞悬液。盐水对照组、细胞移植组大鼠建立脊髓损伤模型,造模成功后1周,细胞移植组经尾静脉注射1mL干细胞悬液,盐水对照组同法注射等体积的生理盐水,模型对照组不做任何处理。结果与结论:与模型对照组和盐水对照组比较,细胞移植组大鼠后肢运动功能明显恢复,BBB评分明显升高(P<0.05);胶质纤维酸性蛋白阳性表达明显减少(P<0.05),神经元特异性烯醇化酶、巢蛋白的阳性表达均明显升高(P<0.05)。移植后3d及1周,在损伤区及临近的脊髓节段可见经荧光染料标记的脂肪间充质干细胞,主要聚集在受损伤脊髓节段1cm范围内,呈不均匀分布。提示急性闭合性脊髓损伤大鼠经尾静脉移植人脂肪间充质干细胞后,其行为学得到改善,受损脊髓节段局部神经元细胞分化明显增多,修复速度加快。

BACKGROUND：As a convenience derived stem cells,adipose-derived mesenchymal stem cells（ADMSCs） have been confirmedthat it can be differentiated into neuron-like cells after induced with inducer like Danshen root in vitro.Therefore,ADMSCs have the possibility to become a new seed cell which can treat spinal cord injury.OBJECTIVE：To explore the effects of tail vein transplantation with ADMSCs on rat behaviors of acute closed spinal cord injury and expressions of various factors in spinal cord tissue.METHODS：Human ADMSCs were isolated and cultured in vitro under sterile conditions.When ADMSCs were transmitted into thefourth generation,the cell concentration was adjusted to 1×109/L.Model of spinal cord injury was established in rats of saline control and cell transplantation groups.At 1 week following model induction,1 mL stem cell suspension was injected into the tail vein of rats from the cell transplantation group.The same volume of saline was injected into the saline control group.No treatmentwas given in the model control group.RESULTS AND CONCLUSION：Compared with the model control group and saline control group,the motor function of the hind limb was significantly recovered in the cell transplantation,but BBB score was significantly increased（P 0.05）.Expression of glialfibrillary acidic protein was significantly decreased（P 0.05）.Positive expression of neuron specific enolase and nestin was significantly increased（P 0.05）.At 3 days and 1 week following transplantation,fluorochrome-labeled ADMSCs were visible in the damaged region and surrounding segments,mainly in 1 cm range of damaged spinal cord segment,showing uneven distribution.These indicated that after the rats which suffered from acute closed spinal cord injury were transplanted via the tail vein with ADMSCs,their behaviors were improved,and the differentiations of neuronal cells were significantly increased in local damaged regions,resulting in rapid repair.