胚胎神经干细胞移植治疗阿尔茨海默病

Embryonic neural stem cell transplantation for Alzheimer's disease

背景:近年来,干细胞疗法得到广泛关注,外源性干细胞通过自我复制及分化补充和替代受损或死亡的神经组织细胞,为神经系统损伤带来了希望。目的:探讨神经干细胞移植治疗阿尔茨海默病的效果。方法:(1)选取30只APP/PS1双转基因AD小鼠,随机分为3组,分别为模型组、细胞液移植组、细胞移植组,每组10只;另选取10只C57BL/6小鼠作为对照组;(2)获取E18的C57BL/6小鼠胚胎,制成神经干细胞悬液,按照感染复数值为1,5,10,15,20加入携带有GFP基因的慢病毒载体稀释液进行神经干细胞转染;(3)根据脑立体定位技术将含有GFP基因的神经干细胞移植到阿尔茨海默病小鼠脑内海马中,细胞液移植组采用上述相同的移植方法注射同体积完全培养基;(4)移植后2周进行Morris水迷宫实验,移植4周后获取大脑标本,进行组织学检测。结果与结论:(1)模型组、细胞移植组、细胞液移植组的潜伏期均显著长于对照组,目标象限次数均显著少于对照组,差异有显著性意义(P<0.05)。细胞移植组的潜伏期显著短于细胞液移植组和模型组,进入目标象限的次数则显著高于上述两组,差异有显著性意义(P<0.05);(2)移植4周后,与模型组比较,细胞移植组神经元形态较为完整,且数量显著增加;(3)结果表明,神经干细胞移植治疗阿尔茨海默病小鼠,可以在行为学和形态学上有所改善。

BACKGROUND： More recently, stem cell therapy has become an issue of concern. Exogenous neural stem cell transplantation brings new hope for the treatment of nervous system injury by self-replication and differentiation to complement and replace damaged or dead nerve cells.OBJECTIVE： To explore the therapeutic efficacy of neural stem cell transplantation on Alzheimer＇s disease.METHODS： Thirty APP/PS1 mice with Alzheimer＇s disease were randomly assigned into model group, cell solution transplantation group or cell transplantation group（n=10 per group）. Another 10 C57BL/6 mice were selected as controls. Embryos of C57BL/6 mice at 18 embryonic days were taken to make neural stem cell suspension followed by transfection using lentiviral vectors carrying GFP gene at different multiplicities of infection（1, 5, 10, 15, 20）. Afterwards, GFP-transfected neural stem cells were implanted into the hippocampus of Alzheimer＇s disease mice in the cell transplantation group, while the same volume of complete medium was injected into the hippocampus of mice in the cell solution transplantation group.Morris water maze test was performed at 2 weeks after cell transplantation, and brain tissues of mice was taken and detected histologically at 4 weeks after cell transplantation.RESULTS AND CONCLUSION： Compared with the control group, the escape latency was significantly higher, and the number of crossings over the target quadrant was lower in the other three groups（P〈0.05）. Compared with the cell solution transplantation and model groups, in contrast, the escape latency was significantly lower, and the number of crossings over the target quadrant was significantly higher in the cell transplantation group（P〈0.05）. Four weeks after transplantation, more intact neurons were found in the cell transplantation group as compared with the model group. These findings indicate that neural stem cell transplantation can improve behavior and morphology performance of mice with Alzheimer＇s disease.