神经干细胞经尾静脉移植后在阿尔茨海默病鼠脑组织中的分布

Study on distribution of neural stem cells in the brain of Alzheimer disease transgenic mice through caudal vein transplantation

目的观察移植的神经干细胞能否顺利通过阿尔茨海默病(AD)转基因小鼠的血脑屏障,以及进一步在其脑内存活与迁徙的规律。方法体外分离培养获得神经干细胞,绿色荧光蛋白标记后通过 AD 鼠尾静脉移植,在移植后48 h,1周、2周,1个月分别取脑连续冰冻切片,荧光显微镜下观察移植细胞的分布以及迁移情况。结果在移植后的不同时间点,脑内均可见到散在分布绿色荧光蛋白阳性细胞,48 h 内以血管周围分布较为常见,随时间延长至4周,海马和脑皮质中也可见弥散分布。而接受移植的小鼠4周内生长发育良好,未见到有成瘤现象发生。结论神经干细胞能够顺利通过阿尔茨海默病转基因小鼠的血脑屏障,在其脑中弥散分布并随时间发生迁移。

Objective To observe whether neural stem cells （NSCs） can successfully permeate into the brain through the blood-brain barrier （BBB） of Alzheimer disease （AD） transgenic mice and explore the methods of distribution and migration. Methods NSCs were isolated from 12-day-old fetal mice, cultured, labeled with enhanced green fluorescent protein （eGFP） and then transplanted into 10 AD transgenic mice and normal mice as controls through caudal vein. The mice were killed 48 h, 1 w, 2 w, and 4 w after transplantation respectively. The brains of the mice were made into continual frozen sections, the distribution and migration of the eGFP-labeled NSCs were studied under fluorescence microscope. Results At different time points after transplantation the eGFP-labeled NSCs were diffusely distributed in the brain： distributed around the blood vessels in the first 48 h, and then migrated gradually towards the hippocampus and cortex until 4 weeks later. There were no obvious abnormal complications occurring after transplantation. Conclusion NSCs can successfully permeate into the brain through the BBB of AD transgenic mice, and migrate into the brain parenchyma gradually.