neural stem cell transplantation for the Parkinson's disease

对于帕金森病（PD）实现神经干细胞脑内替代治疗，我们假设神经干细胞自体移植（NSCs）是最安全和最有用的治疗方法之一。我们发现：首先，从成年啮齿动物或灵长类动物的心室下区获取神经干细胞，在增殖因子的存在下扩增到可移植的细胞数量，并在酪氨酸羟化酶诱导因子的作用下分化成大量多巴胺能神经元。成人NSCs移植具有行为学和组织学改善的神经保护作用。其机制是成体NSCs能够分泌多种神经营养因子和细胞因子（GDNF、EPO、CNTF等），对移植纹状体周围产生影响。第三，我们利用GDNF基因转染的方法，建立了对多巴胺能神经元具有最大神经营养作用的GDNF，生成NSCs （NSC-G…More DNF）。NSC-GDNF移植对帕金森病模型动物具有行为学和组织学改善的神经保护作用。NSC-GDNF分泌的GDNF对移植物细胞具有较强的存活和迁移作用。其机制是，NSC-GDNF移植可改变受损纹状体的微环境，而被安置的宿主胶质细胞可释放除GDNF外的其他营养因子。最后，移植来自成人NSCs的多巴胺能（DA）神经元对帕金森大鼠模型具有恢复作用。神经干细胞来源的DA神经元在受损纹状体中存活较差，但移植的DA神经元与宿主神经元之间形成大量突触。其机制是上调BDNF和磷酸化CREB可促进突触发生。这些结果提示自体成体神经干细胞移植是治疗帕金森病的有效方法。少

For Parkinson's disease (PD) to realize intracerebral cell replacement therapy using neural stem cells, we hypothesized that autologous transplantation using neural stem cells (NSCs) is one of the safest and most useful therapies.We showed the following:First, neural stem cells were harvested from the subventricular zone of adult rodents or primates, were expanded to the transplantable number of cells in the presence of proliferating factors, and could be differentiated into a large number of dopaminergic neurons using tyrosine hydroxylase-inducing factor.Second, transplantation of adult NSCs had the neuroprotective effects as the behavioral and histological improvements. The mechanism is that adult NSCs could secrete the various kinds of neurotrophic factors and cytokines (GDNF, EPO, CNTF etc), which had the effects surrounding to the transplanted striatum.Third, We established the GDNF, which has a one of the most neurotrophic effect on the dopaminergic neurons, producing NSCs (NSC-G … More DNF) using GDNF gene transfection method. The transplantation of NSC-GDNF had a neuroprotective effect in the parkinsonian model animals as the behavioral and histological improvements. GDNF secreted from NSC-GDNF also had a strong surviving and migrating effect for the grafted cells and migrating. The mechanism is that NSC-GDNF transplantation may change the microenvironment into the lesioned striatum and the accommodated host glial cells may release the other trophic factors except for GDNF.Finally, transplantation of dopaminergic (DA) neurons derived from adult NSCs has a restorative effect for the parkinsonian rat model. The survival of the grafted DA neurons derived from NSCs was poor in the lesioned striatum, but the great number of synapse formation between the grafted DA neurons and host neurons were observed. The mechanism is that upregulation of BDNF and phosphorylated CREB may enhance the synaptogenesis.These results suggested that autologous transplantation of adult neural stem cells is useful in the treatment of PD. Less