脐带间充质干细胞移植治疗大鼠脑缺血损伤

背景:对于缺血性脑卒中至今尚无确实有效的药物治疗,干细胞因其具有高度自我更新能力和多向分化潜能,使其重建中枢神经系统结构与功能成为可能。目的:观察脐带间充质干细胞移植治疗缺血性脑卒中模型鼠的效果及安全性,并探讨其可能机制。方法:体外分离人脐带间充质干细胞,移植前以BrdU标记。将SD雄性大鼠制作大脑中动脉闭塞模型后随机分为3组:移植组于造模后第7天,移植脐带间充质干细胞到损伤侧纹状体,PBS组给予等量PBS,模型组大鼠不做处理。结果与结论:①人脐带间充质干细胞移植组大鼠mNSS评分恢复优于模型组(P<0.05);模型组mNSS评分在损伤后35d内恢复速度慢于模型组(P<0.05),至第56天与模型组比较差异无显著性意义(P>0.05)。②移植组大鼠损伤中心及周围均可见Brdu染色阳性细胞及与Nestin、微管缔合蛋白2、胶原纤维酸性蛋白、Ⅷ因子、血管内皮生长因子免疫组织化学双染阳性细胞。表明脐带间充质干细胞可以在体外分离培养,移植后能在鼠宿主脑内存活、分化,促进大脑中动脉闭塞模型鼠神经功能的恢复。推测其机制可能与移植后细胞分化为神经元样和神经胶质细胞样细胞,并分泌或促进宿主分泌神经营养因子、促进新生血管形成有关。

Umbilical cord blood mesenchymal stem cells transplantation for the treatment of cerebral ischemia injury in rats

BACKGROUND: There is yet no medicine that is confirmed to improve ischemic stroke. The high self-renewal ability and multiplex differentiation potential make it possible for stem cells to rebuild the structure and function of the central nervous system (CNS). OBJECTIVE: To observe the effect and safety of umbilical cord blood mesenchymal stem cells transplantation for the treatment of ischemic stroke in rat models and to investigate its possible mechanism. METHODS:Human umbilical cord blood mesenchymal stem cells were isolated in vitro by using density gradient centrifugation combined with adherent screening and labeled by BrdU before transplantation. The male SD rats were used to establish the middle cerebral artery occlusion model and then the models were randomly divided into 3 groups. In the transplantation group, the umbilical cord blood mesenchymal stem cells were transplanted into corpus striatum on the injury side at 7 days after modeling; the PBS group was given the same dose of PBS and the rats in model group were without treatment. RESULTS AND CONCLUSION: The recovery of mNSS score of transplantation group was better than that of model group (P < 0.05), and the recovery of mNSS score in PBS group was slower than that in model group within 35 days (P < 0.05), and had no significant difference at the 56th day (P > 0.05). BrdU staining positive cells and Nestin, microtubule rapsyn 2, glial fibrillary acidic protein, Ⅷ factor and vascular endothelial growth factor immunohistochemical double staining positive cells could be seen in the center and surroundings of the injury area in transplantation group. It indicated that umbilical cord blood mesenchymal stem cells could be isolated in vitro, and could survive and differentiate in rat host brain and promote the recovery of the neural function of middle cerebral artery occlusion model rats. The mechanism might be related to the transplanted cells differentiating into neuron-like and neural glial-like cells, and secreting neurotrophic factors and promoting angiogenesis of host cells.