神经干细胞移植治疗大鼠局灶性脑缺血损伤

背景：近年来,神经干细胞移植已成为治疗神经退行性疾病和中枢神经系统损伤的研究热点。目的：探讨神经干细的定向分化调控机制和神经干细胞移植治疗大鼠局灶性脑缺血损伤的研究进展。方法：以＂neural stem cells,stem cell transplantation,ischemic brain injury＂为检索词,检索Pubmed数据库1990至2012年相关文献;以＂神经干细胞,干细胞移植,缺血性脑损伤＂为检索词,检索CNKI数据库2005至2012年相关文献。分析神经干细的定向分化调控机制和神经干细胞移植治疗大鼠局灶性脑缺血损伤的内容,排除重复研究。结果与结论：①体外分离培养的神经干细胞有胚胎来源、脐血来源和成体来源,主要采用机械分离法和胰酶消化法进行分离。②目前体外培养的神经干细胞分离鉴定的标记物有巢蛋白、波形蛋白1、5-溴脱氧尿嘧啶核苷、神经元特异性烯醇化酶等。③神经干细胞的分化调节是通过正负双重作用实现的,负性调节是通过对称性的分裂来增加神经干细胞数量,包括Notch信号途径和一些生长因子等。正性调节诱导神经干细胞分化,包括参与细胞合成的骨形态发生蛋白信号途径等。④神经干细胞移植的时间窗选择在实验动物脑缺血两三周后,时间过早和过晚均不适合细胞的存活。神经干细胞通过脑立体定位仪直接进行脑内移植治疗大鼠局灶性脑缺血损伤,移植后可见细胞在局灶性脑缺血大鼠脑室内和梗死中心均可长期存活,并可广泛迁移,移植神经干细胞后观察到其运动行为学评分有明显提高。缺血性脑卒中的神经干细胞移植治疗还存在一些问题需要解决,未来的临床应用前景广阔,是缺血性脑卒中患者的新希望。

Neural stem cell transplantation for treatment of focal cerebral ischemia injury in rats

BACKGROUND： In recent years, neural stem cell transplantation for the treatment of neurodegenerative diseases and central nervous system injury has become the research focus. OBJECTIVE： To investigate the research progress of directed differentiation regulation mechanism of neural stem cells and neural stem cell transplantation for the treatment of focal cerebral ischemia injury. METHODS： The PubMed database and CNKI database were searched for the related articles from 2005 to 2012 with the key words＂neural stem cells, stem cell transplantation, ischemic brain injury＂ in English and Chinese. The articles on the directed differentiation regulation mechanism of neural stem cells and neural stem cell transplantation for the treatment of focal cerebral ischemia injury were selected, and the repetitive articles were eliminated. RESULTS AND CONCLUSION： The in vitro isolated and cultured neural stem cells included embryo-derived stem cells, umbilical cord blood-derived stem cells and adult-derived stem cells, and the stem cells were mainly isolated with mechanical separation and trypsin digestion methods. At present, the makers used to identify the in vitro cultured neural stem cells included nestin, vimentin 1, 5-bromodeoxyuridine and neuron-specific enolase. The differentiation of the neural stem cells could be achieved through the positive and negative regulation, and the negative regulation could increase the number of neural stem cells through symmetry splitting, including the Notch signaling pathway and other growth factors, while the positive regulation could induce the differentiation of neural stem cells, such as the bone morphogenetic protein signaling pathways involved in cell synthesis. The best time to neural stem cell transplantation was 2-3 weeks after brain ischemia, and it was not suitable for cell survival when transplanted too early and too late. Neural stem cell transplantation through brain stereotaxic instrument had positive effect on the treatment of focal cerebral ischemia injury. The neural stem cells could long-term survive in the ventricle and infarct center of rats with focal cerebral ischemia and the cells could migrate widely. Motion behavior scores were significantly increased after neural stem cell transplantation. The neural stem cell transplantation for the treatment of ischemic stroke still need to be searched, but the neural stem cell transplantation had wide clinical application prospects in the future which is considered as the new hope for the patients with ischemic stroke.