Department of Physiology, Keio University School of Medicine, Shinanomachi,Shinjuku-ku, Tokyo, Japan.
Proc Jpn Acad Ser B Phys Biol Sci. 2010;86(4):438-50. doi: 10.2183/pjab.86.438.
The adult mammalian central nervous system (CNS), especially that of adult humans, is a representative example of organs that do not regenerate. However, increasing interest has focused on the development of innovative therapeutic methods that aim to regenerate damaged CNS tissue by taking advantage of recent advances in stem cell and neuroscience research. In fact, the recapitulation of normal neural development has become a vital strategy for CNS regeneration. Normal CNS development is initiated by the induction of stem cells in the CNS, i.e., neural stem cells (NSCs). Thus, the introduction or mobilization of NSCs could be expected to lead to CNS regeneration by recapitulating normal CNS development, in terms of the activation of the endogenous regenerative capacity and cell transplantation therapy. Here, the recent progress in basic stem cell biology, including the author's own studies, on the prospective identification of NSCs, the elucidation of the mechanisms of ontogenic changes in the differentiation potential of NSCs, the induction of neural fate and NSCs from pluripotent stem cells, and their therapeutic applications are summarized. These lines of research will, hopefully, contribute to a basic understanding of the nature of NSCs, which should in turn lead to feasible strategies for the development of ideal "stem cell therapies" for the treatment of damaged brain and spinal cord tissue.
成年哺乳动物中枢神经系统(CNS),特别是成年人类的 CNS,是一个不会再生的器官的典型代表。然而,人们越来越关注开发创新的治疗方法,利用干细胞和神经科学研究的最新进展,旨在再生受损的中枢神经系统组织。事实上,再现正常的神经发育已成为中枢神经系统再生的重要策略。正常的中枢神经系统发育是由中枢神经系统中的干细胞诱导启动的,即神经干细胞(NSCs)。因此,通过内源性再生能力的激活和细胞移植治疗,引入或动员 NSCs 有望通过再现正常的中枢神经系统发育来实现中枢神经系统的再生。在这里,总结了基础干细胞生物学的最新进展,包括作者自己的研究,关于 NSCs 的预期鉴定、NSCs 分化潜能的个体发生变化的机制的阐明、诱导多能干细胞向神经命运和 NSCs 的分化,以及它们的治疗应用。这些研究将有助于深入了解 NSCs 的本质,这反过来又将为开发理想的“干细胞疗法”以治疗受损的大脑和脊髓组织提供可行的策略。