Xu Zhimin, Chu Xingkun, Jiang Houbo, Schilling Haley, Chen Shengdi, Feng Jian
Veterans Affairs Western New York Healthcare System, Buffalo, NY 14215, USA; Department of Physiology and Biophysics, State University of New York at Buffalo, Buffalo, NY 14214, USA; Laboratory of Neurodegenerative Diseases, Institute of Health Science, Shanghai Institutes for Biological Sciences, Chinese Academy of Science and Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Laboratory of Neurodegenerative Diseases, Institute of Health Science, Shanghai Institutes for Biological Sciences, Chinese Academy of Science and Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Redox Biol. 2017 Apr;11:606-612. doi: 10.1016/j.redox.2017.01.009. Epub 2017 Jan 16.
Motor symptoms that define Parkinson's disease (PD) are caused by the selective loss of nigral dopaminergic (DA) neurons. Cell replacement therapy for PD has been focused on midbrain DA neurons derived from human fetal mesencephalic tissue, human embryonic stem cells (hESC) or human induced pluripotent stem cells (iPSC). Recent development in the direct conversion of human fibroblasts to induced dopaminergic (iDA) neurons offers new opportunities for transplantation study and disease modeling in PD. The iDA neurons are generated directly from human fibroblasts in a short period of time, bypassing lengthy differentiation process from human pluripotent stem cells and the concern for potentially tumorigenic mitotic cells. They exhibit functional dopaminergic neurotransmission and relieve locomotor symptoms in animal models of Parkinson's disease. In this review, we will discuss this recent development and its implications to Parkinson's disease research and therapy.
定义帕金森病(PD)的运动症状是由黑质多巴胺能(DA)神经元的选择性丧失引起的。PD的细胞替代疗法一直集中于源自人类胎儿中脑组织、人类胚胎干细胞(hESC)或人类诱导多能干细胞(iPSC)的中脑DA神经元。人类成纤维细胞直接转化为诱导多巴胺能(iDA)神经元的最新进展为PD的移植研究和疾病建模提供了新机会。iDA神经元在短时间内直接从人类成纤维细胞产生,绕过了从人类多能干细胞开始的漫长分化过程以及对潜在致瘤性有丝分裂细胞的担忧。它们在帕金森病动物模型中表现出功能性多巴胺能神经传递并缓解运动症状。在这篇综述中,我们将讨论这一最新进展及其对帕金森病研究和治疗的意义。