The North Bay CIRM Shared Research Laboratory for Stem Cells and Aging, Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945, USA.
J Cell Biochem. 2012 Dec;113(12):3610-9. doi: 10.1002/jcb.24251.
Parkinson's disease (PD) is the second most common neurodegenerative disorder. The motor symptoms of PD are caused by the loss of dopaminergic (DA) neurons in the substantia nigra pars compacta of mesencephalon. The causes for death of DA neurons are not well understood, but the strongest risk factor is increasing age. There is no cure currently available for PD, and treatment is limited to management of PD symptoms in patients. Primary DA neurons are virtually unobtainable from living patients and animal studies have proven inadequate for studying the mechanism of PD development. Pluripotent stem cells (PSC) are primary self-renewing cells capable of differentiating into all cell types of an organism, including DA neurons. PSCs represent an abundant source of cells that can be genetically modified or isolated from patients with complex diseases, enabling the production of large quantities of DA neurons for disease modeling, drug screening, and gene function studies. Furthermore, since PD arises as a result of deterioration of DA neurons in a specific brain region, it has been suggested that a relatively small number of cells could restore normal function. PSCs could provide a source of DA neurons for cell replacement therapy. In this Prospects article, we focus on the development and in vitro derivation of DA neurons from PSCs, as well as current applications of the technological advances, with the emphasis on future directions and efforts in the field.
帕金森病（PD）是第二常见的神经退行性疾病。PD 的运动症状是由中脑黑质致密部的多巴胺能（DA）神经元丧失引起的。导致 DA 神经元死亡的原因尚不清楚，但最强的危险因素是年龄的增长。目前 PD 尚无治愈方法，治疗仅限于管理患者的 PD 症状。来自活患者的原发性 DA 神经元几乎无法获得，并且动物研究已证明不足以研究 PD 发展的机制。多能干细胞（PSC）是能够分化为生物体所有细胞类型的主要自我更新细胞，包括 DA 神经元。PSC 是一种丰富的细胞来源，可以对患有复杂疾病的患者进行基因修饰或分离，从而能够大量产生 DA 神经元用于疾病建模、药物筛选和基因功能研究。此外，由于 PD 是由于特定脑区的 DA 神经元退化引起的，因此有人认为相对较少的细胞就可以恢复正常功能。PSC 可以为细胞替代疗法提供 DA 神经元的来源。在这篇展望文章中，我们重点介绍了 PSC 中 DA 神经元的发育和体外分化，以及技术进步的当前应用，重点介绍了该领域的未来方向和努力。
