促红细胞生成素基因修饰脐带间充质干细胞移植颅脑损伤大鼠脑细胞形态及神经功能的恢复

Therapeutic effect of erythropoietin gene modified umbilical cord derived mesenchymal stem cells transplantation on the morphology of brain cells and the recovery of neurological function in traumatic brain injury rats

背景：很多研究表明,促红细胞生成素具有神经保护作用。目的：探讨促红细胞生成素修饰的脐带间充质干细胞脑内移植对脑损伤大鼠脑损伤的治疗效果。方法：用Westernblot鉴定外源人促红细胞生成素基因在脐带间充质干细胞中的表达。90只大鼠成功建立重型液压颅脑损伤模型,随机数字表法均分成为对照组、脐带间充质干细胞移植组、促红细胞生成素＋脐带间充质干细胞移植组。结果与结论：Westernblot结果显示转染人促红细胞生成素基因的人脐带间充质干细胞体外能表达促红细胞生成素;与对照组比较,移植后1,2,3,4周脐带间充质干细胞移植组、促红细胞生成素＋脐带间充质干细胞移植组大鼠神经缺损评分均降低（P〈0.05）,后者更低（P〈0.01）。各组平均潜伏时间均逐渐缩短,3-5d时平均潜伏时间为促红细胞生成素＋脐带间充质干细胞移植组〈脐带间充质干细胞移植组（P〈0.05）〈对照组（P〈0.01）。穿越平台次数及在目标象限游泳距离与总距离百分促红细胞生成素＋脐带间充质干细胞移植组最高（P〈0.05）。形态学可见3组损伤处脑组织瘢痕和软化灶为：促红细胞生成素＋脐带间充质干细胞移植组〈脐带间充质干细胞移植组〈对照组,CM-Dil阳性细胞数则3组相反。说明促红细胞生成素修饰的脐带间充质干细胞脑内移植后对脑损伤大鼠脑损伤具有较好的治疗作用。

BACKGROUND： Many studies have shown that erythropoietin （EPO） has a neuroprotective effect. OBJECTIVE： To investigate the therapeutic effect of EPO modified human umbilical cord derived mesenchymal stem cells （UC-MSCs） intracerebral transplantation on traumatic brain injury of rats. METHODS： The expression of exogenous EPO in UC-MSCs was examined by Western blot. 90 healthy Wistar rats were used to establish the heavy-duty hydraulic model of traumatic brain injury. The models were randomly divided into control group, UC-MSCs transplantation group and EPO＋UC-MSCs transplantation group. RESULTS AND CONCLUSION： Western blot results showed that the EPO gene modified UC-MSCs could express the EPO in vitro. Compared with control group, the neurological severity scores （mNSS） in UC-MSCs transplantation group and EPO＋UC-MSCs transplantation group was decreased （P〈0.05） and lower in EPO＋UC-MSCs transplantation group （P〈0.01）. The average time of escape latency was gradually decreased in each group. However, from the 3rd to the 5th day, time in EPO＋UC-MSCs transplantation group was shorter than that in control group （P〈0.05） and then in UC-MSCs group （P〈0.01）. In addition, the frequency of platform passing and the percentage of swimming distance in target quadrant and total distance was highest in EP0＋UC-MSCs transplantation group （P〈0.05）. Morphological observation showed that the scar and malacia of brain tissue in EPO＋UC-MSCs transplantation group was smaller than that in UC-MSCs transplantation group and then in control group, but the sequence of the CM-Dil positive cells number in three groups was contrast. Transplantation of EPO gene-modified UC-MSCs can significantly improve the neurological function in the rats with TBI.