Department of Animal Science, Cornell University, Ithaca, NY 14853, USA.
Front Biosci (Landmark Ed). 2012 Jan 1;17(1):65-89. doi: 10.2741/3916.
Research on the biology of adult stem cells, embryonic stem cells and induced pluripotent stem cells, as well as cell-based strategies for treating nervous system disorders has begun to create the hope that these cells may be used for therapy in humans after injury or disease. In animal models of neurological diseases, transplantation of stem cells or their derivatives can improve function not only due to direct replacement of lost neurons or glia, but also by providing trophic support. Despite intense research efforts to translate these studies from the bench to bedside, critical problems remain at several steps in this process. Recent technological advancements in both the derivation of stem cells and their directed differentiation to lineage-committed progenitors have brought us closer to therapeutic applications. Several preclinical studies have already explored the behavior of transplanted cells with respect to proliferation, migration, differentiation and survival, especially in complex pathological disease environments. In this review, we examine the current status, progress, pitfalls, and potential of these stem cell technologies, focusing on directed differentiation of human stem cells into various neural lineages, including dopaminergic neurons, motor neurons, oligodendroglia, microglia, and astroglia, and on advancements in cell-based regenerative strategies for neural repair and criteria for successful therapeutic applications.
对成体干细胞、胚胎干细胞和诱导多能干细胞的生物学研究,以及基于细胞的治疗神经系统疾病策略的研究,已经开始带来希望,即这些细胞在人类受伤或患病后可能被用于治疗。在神经疾病的动物模型中,干细胞或其衍生物的移植不仅可以通过直接替代丧失的神经元或神经胶质细胞来改善功能,还可以通过提供营养支持来改善功能。尽管在将这些研究从实验室转化为临床应用方面进行了大量研究,但在这个过程的几个步骤中仍然存在关键问题。在干细胞的诱导及其向谱系定向祖细胞的定向分化方面的最近技术进步,使我们更接近治疗应用。一些临床前研究已经探索了移植细胞的行为,包括增殖、迁移、分化和存活,特别是在复杂的病理性疾病环境中。在这篇综述中,我们检查了这些干细胞技术的现状、进展、陷阱和潜力,重点是将人类干细胞定向分化为各种神经谱系,包括多巴胺能神经元、运动神经元、少突胶质细胞、小胶质细胞和星形胶质细胞,以及基于细胞的神经修复再生策略的进展和成功治疗应用的标准。