Qiu Zhifang, Farnsworth Steven L, Mishra Anuja, Hornsby Peter J
Geriatric Research Education and Clinical Center, South Texas Veterans Health Care System, San Antonio, TX, USA ; Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center, San Antonio, TX, USA.
Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center, San Antonio, TX, USA.
Stem Cells Cloning. 2013 Jul 3;6:19-29. doi: 10.2147/SCCAA.S34798.
The development of the technology for derivation of induced pluripotent stem (iPS) cells from human patients and animal models has opened up new pathways to the better understanding of many human diseases, and has created new opportunities for therapeutic approaches. Here, we consider one important neurological disease, Parkinson's, the development of relevant neural cell lines for studying this disease, and the animal models that are available for testing the survival and function of the cells, following transplantation into the central nervous system. Rapid progress has been made recently in the application of protocols for neuroectoderm differentiation and neural patterning of pluripotent stem cells. These developments have resulted in the ability to produce large numbers of dopaminergic neurons with midbrain characteristics for further study. These cells have been shown to be functional in both rodent and nonhuman primate (NHP) models of Parkinson's disease. Patient-specific iPS cells and derived dopaminergic neurons have been developed, in particular from patients with genetic causes of Parkinson's disease. For complete modeling of the disease, it is proposed that the introduction of genetic changes into NHP iPS cells, followed by studying the phenotype of the genetic change in cells transplanted into the NHP as host animal, will yield new insights into disease processes not possible with rodent models alone.
从人类患者和动物模型中诱导多能干细胞（iPS细胞）的技术发展，为更好地理解多种人类疾病开辟了新途径，并为治疗方法创造了新机会。在此，我们探讨一种重要的神经疾病——帕金森病，以及用于研究该疾病的相关神经细胞系的发展，还有将细胞移植到中枢神经系统后用于测试细胞存活和功能的动物模型。最近，在多能干细胞的神经外胚层分化和神经模式形成方案的应用方面取得了快速进展。这些进展使得能够产生大量具有中脑特征的多巴胺能神经元以供进一步研究。这些细胞在帕金森病的啮齿动物和非人类灵长类动物（NHP）模型中均已显示出功能。特别是从患有帕金森病遗传病因的患者中，已经培养出了患者特异性的iPS细胞及其衍生的多巴胺能神经元。为了对该疾病进行完整建模，有人提出将基因改变引入NHP的iPS细胞，然后研究移植到作为宿主动物的NHP体内的细胞中基因改变的表型，这将为仅用啮齿动物模型无法实现的疾病过程带来新见解。
