Flax J D, Aurora S, Yang C, Simonin C, Wills A M, Billinghurst L L, Jendoubi M, Sidman R L, Wolfe J H, Kim S U, Snyder E Y
Department of Neurology, Children's Hospital, Harvard Medical School, Boston, MA, USA.
Nat Biotechnol. 1998 Nov;16(11):1033-9. doi: 10.1038/3473.
Stable clones of neural stem cells (NSCs) have been isolated from the human fetal telencephalon. These self-renewing clones give rise to all fundamental neural lineages in vitro. Following transplantation into germinal zones of the newborn mouse brain they participate in aspects of normal development, including migration along established migratory pathways to disseminated central nervous system regions, differentiation into multiple developmentally and regionally appropriate cell types, and nondisruptive interspersion with host progenitors and their progeny. These human NSCs can be genetically engineered and are capable of expressing foreign transgenes in vivo. Supporting their gene therapy potential, secretory products from NSCs can correct a prototypical genetic metabolic defect in neurons and glia in vitro. The human NSCs can also replace specific deficient neuronal populations. Cryopreservable human NSCs may be propagated by both epigenetic and genetic means that are comparably safe and effective. By analogy to rodent NSCs, these observations may allow the development of NSC transplantation for a range of disorders.
已从人类胎儿端脑中分离出神经干细胞（NSCs）的稳定克隆。这些自我更新的克隆在体外可产生所有基本的神经谱系。移植到新生小鼠脑的生发区后，它们参与正常发育的多个方面，包括沿着既定的迁移途径迁移到中枢神经系统的各个区域、分化为多种在发育和区域上合适的细胞类型，以及与宿主祖细胞及其后代无干扰地相互散布。这些人类神经干细胞可以进行基因工程改造，并能够在体内表达外源转基因。支持其基因治疗潜力的是，神经干细胞的分泌产物可在体外纠正神经元和神经胶质细胞中的典型遗传代谢缺陷。人类神经干细胞还可以替代特定的缺陷神经元群体。可冷冻保存的人类神经干细胞可以通过表观遗传和遗传手段进行增殖，这些手段同样安全有效。类似于啮齿动物神经干细胞，这些观察结果可能有助于开发针对一系列疾病的神经干细胞移植疗法。
