重编程多能干细胞构建组织工程化神经移植修复脑损伤的实验研究

Application of reprogrammed multipotent stem cells modified by tissue engineering in repairing traumatic brain injury

目的利用重编程多能干细胞构建组织工程化神经,探讨组织工程化神经移植治疗大鼠脑损伤的作用和机制。方法采用改良Feeney自由落体法对80只雄性SD大鼠建立脑创伤模型后,将其随机分成4组:损伤对照组(A组),单纯组织工程细胞支架组(B组),单纯脂肪干细胞组(C组)和组织工程化神经组(D组)。移植后采用动物神经缺损体征评分、Morris水迷宫试验,以及脑组织病理检查评估大鼠神经功能的修复状况。结果重编程多能干细胞可显著表达神经元标记物(Neu N)。移植后2周,组织工程化神经组大鼠的神经缺损体征评分明显低于其他各组,并且Morris水迷宫试验平均逃避潜伏期明显缩短,穿越平台次数明显增多。移植后4周,病理检查结果示,组织工程化神经组大鼠的脑组织无明显空洞和软化灶,同时出现典型的神经细胞样形态学改变。结论重编程多能干细胞构建的组织工程化神经能够明显改善脑损伤大鼠的神经功能。

Objective To establish the tissue-engineered neural complex by reprogrammed multipotent stem cells and to investigate therapeutic effects of tissue-engineered neural complex in a rat model of traumatic brain injury（TBI）.Methods TBI models of Sprague-Dawley（SD） rats were established by using Feeney’s free-falling epidural impact model.A total of 80 male SD rats were randomly and equally divided into 4 groups,i.e.traumatic brain injury control group（group A）,PLGA control group（group B）,adipose-derived stem cell group（group C） and tissue-engineered neural complex group（group D）.The neurological defect scores,the Morris water maze test and Haematoxylin-eosin（HE） staining were performed to evaluate the recovery of neurological function in the rats.Results The significant expression of Neu N were found in the reprogrammed multipotent stem cells.At 2 weeks after transplantation,neurological defect scores was significantly less in tissueengineered neural complex group compared with other groups.Moreover,the MWM test showed that the least of average incubation period and the most of times for crossing platform were happened in tissue-engineered neural complex group.At 4 weeks after transplantation,HE staining showed that typical morphological changes as neural cells with cavity in tissue-engineered neural complex group.Conclusion Tissue engineered neural complex after transplantation can significantly improve the neurological function in rats with TBI.