Lee Il-Shin, Jung Kwangsoo, Kim Miri, Park Kook In
Department of Pediatrics and BK21 Project for Medical Sciences, Yonsei University College of Medicine, Severance Children's Hospital, Seoul, Korea.
Pediatr Int. 2010 Dec;52(6):855-65. doi: 10.1111/j.1442-200X.2010.03266.x.
Neural stem cells (NSCs) are defined by their ability to self-renew, to differentiate into cells of all glial and neuronal lineages throughout the neuraxis, and to populate developing or degenerating central nervous system (CNS) regions. The recognition that NSCs propagated in culture could be reimplanted into the mammalian brain, where they might integrate appropriately throughout the mammalian CNS and stably express foreign genes, has unveiled a new role for neural transplantation and gene therapy and a possible strategy for addressing the CNS manifestations of diseases that hitherto had been refractory to intervention. An intriguing phenomenon with possible therapeutic potentials has begun to emerge from our observations of the behavior of NSCs in animal models of neonatal hypoxic-ischemic (HI) brain injury. During phases of active neurodegeneration, factors seem to be transiently elaborated to which NSCs may respond by migrating to degenerating regions and differentiating specifically towards replacement of dying neural cells. NSCs may attempt to repopulate and reconstitute ablated regions. These 'repair mechanisms' may actually reflect the reexpression of basic developmental principles that may be harnessed for therapeutic ends. In addition, NSCs may serve as vehicles for gene delivery and appear capable of simultaneous neural cell replacement and gene therapy (e.g. with factors that might enhance neuronal differentiation, neurites outgrowth, proper connectivity, and/or neuroprotection). When combined with certain synthetic biomaterials, NSCs may be even more effective in 'engineering' the damaged CNS towards reconstitution. We have also cultured human NSCs or progenitors as neurospheres which were derived from fetal cadavers at 13 weeks of gestation, and transplanted them into HI-injured immature brains to investigate their therapeutic potentials in this type of model.
神经干细胞（NSCs）的定义是具有自我更新能力，能够分化为整个神经轴所有神经胶质和神经元谱系的细胞，并能在发育中的或退化的中枢神经系统（CNS）区域定植。人们认识到，在培养中繁殖的神经干细胞可以重新植入哺乳动物大脑，在那里它们可能会在整个哺乳动物中枢神经系统中适当整合并稳定表达外源基因，这揭示了神经移植和基因治疗的新作用，以及一种可能的策略来解决迄今为止难以干预的中枢神经系统疾病表现。我们对新生缺氧缺血（HI）脑损伤动物模型中神经干细胞行为的观察开始出现一种具有潜在治疗潜力的有趣现象。在活跃的神经变性阶段，似乎会短暂地产生一些因子，神经干细胞可能会对这些因子做出反应，迁移到退化区域并特异性地分化以替代死亡的神经细胞。神经干细胞可能试图重新填充和重建被切除的区域。这些“修复机制”实际上可能反映了基本发育原则的重新表达，而这些原则可用于治疗目的。此外，神经干细胞可以作为基因传递的载体，并且似乎能够同时进行神经细胞替代和基因治疗（例如使用可能增强神经元分化、神经突生长、适当连接和/或神经保护的因子）。当与某些合成生物材料结合时，神经干细胞在“工程化”受损中枢神经系统以实现重建方面可能会更有效。我们还将源自妊娠13周胎儿尸体的人神经干细胞或祖细胞培养成神经球，并将它们移植到HI损伤的未成熟大脑中，以研究它们在这种模型中的治疗潜力。
