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本文引用的文献

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NTera2: a model system to study dopaminergic differentiation of human embryonic stem cells.NTera2：一种用于研究人类胚胎干细胞多巴胺能分化的模型系统。
Stem Cells Dev. 2005 Oct;14(5):517-34. doi: 10.1089/scd.2005.14.517.
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Directed differentiation of dopaminergic neuronal subtypes from human embryonic stem cells.从人胚胎干细胞定向分化出多巴胺能神经元亚型。
Stem Cells. 2005 Jun-Jul;23(6):781-90. doi: 10.1634/stemcells.2004-0365.
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Collection of neural inducing factors from PA6 cells using heparin solution and their immobilization on plastic culture dishes for the induction of neurons from embryonic stem cells.使用肝素溶液从PA6细胞中收集神经诱导因子，并将其固定在塑料培养皿上以诱导胚胎干细胞分化为神经元。
Biomaterials. 2005 Oct;26(28):5746-54. doi: 10.1016/j.biomaterials.2005.02.021. Epub 2005 Apr 18.
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Karyotypic stability, genotyping, differentiation, feeder-free maintenance, and gene expression sampling in three human embryonic stem cell lines derived prior to August 9, 2001.2001年8月9日之前获得的三个人类胚胎干细胞系的核型稳定性、基因分型、分化、无饲养层培养及基因表达取样。
Stem Cells Dev. 2004 Dec;13(6):585-97. doi: 10.1089/scd.2004.13.585.
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Dopaminergic differentiation of human embryonic stem cells.人胚胎干细胞的多巴胺能分化
Stem Cells. 2004;22(6):925-40. doi: 10.1634/stemcells.22-6-925.
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Generation of tyrosine hydroxylase positive neurons from human embryonic stem cells after coculture with cellular substrates and exposure to GDNF.人胚胎干细胞与细胞基质共培养并暴露于胶质细胞源性神经营养因子（GDNF）后生成酪氨酸羟化酶阳性神经元。
Stem Cells. 2004;22(5):669-74. doi: 10.1634/stemcells.22-5-669.
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Nanometer size diesel exhaust particles are selectively toxic to dopaminergic neurons: the role of microglia, phagocytosis, and NADPH oxidase.纳米级柴油废气颗粒对多巴胺能神经元具有选择性毒性：小胶质细胞、吞噬作用和NADPH氧化酶的作用。
FASEB J. 2004 Oct;18(13):1618-20. doi: 10.1096/fj.04-1945fje. Epub 2004 Aug 19.
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Derivation of midbrain dopamine neurons from human embryonic stem cells.源自人类胚胎干细胞的中脑多巴胺神经元
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Properties of pluripotent human embryonic stem cells BG01 and BG02.多能性人类胚胎干细胞BG01和BG02的特性。
Stem Cells. 2004;22(3):292-312. doi: 10.1634/stemcells.22-3-292.
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GDNF promotes neuronal differentiation and dopaminergic development of mouse mesencephalic neurospheres.胶质细胞源性神经营养因子促进小鼠中脑神经球的神经元分化和多巴胺能发育。
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源自胚胎干细胞的人多巴胺能神经元的体外模型：1-甲基-4-苯基吡啶离子（MPP+）毒性与胶质细胞源性神经营养因子（GDNF）的神经保护作用

An in vitro model of human dopaminergic neurons derived from embryonic stem cells: MPP+ toxicity and GDNF neuroprotection.

作者信息

Zeng Xianmin, Chen Jia, Deng Xiaolin, Liu Ying, Rao Mahendra S, Cadet Jean-Lud, Freed William J

机构信息

Intramural Research Program (IRP), Cellular Neurobiology Research Branch, Department of Health and Human Services (DHHS), National Institute on Drug Abuse (NIDA), National Institutes of Health (NIH), Baltimore, MD, USA.

出版信息

Neuropsychopharmacology. 2006 Dec;31(12):2708-15. doi: 10.1038/sj.npp.1301125.

DOI:10.1038/sj.npp.1301125
PMID:17109014
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1852423/
Abstract

Human embryonic stem cells (hESCs) can proliferate indefinitely yet also differentiate in vitro, allowing normal human neurons to be generated in unlimited numbers. Here, we describe the development of an in vitro neurotoxicity assay using human dopaminergic neurons derived from hESCs. We showed that the dopaminergic neurotoxin 1-methyl-4-phenylpyridinium (MPP(+)), which produces features of Parkinson's disease in humans, was toxic for hESC-derived dopaminergic neurons. Treatment with glial cell line-derived neurotrophic factor protected tyrosine hydroxylase-positive neurons against MPP(+)-induced apoptotic cell death and loss of neuronal processes as well as against the formation of intracellular reactive oxygen species. The availability of human dopaminergic neurons, derived from hESCs, therefore allows for the possibility of directly examining the unique features of human dopaminergic neurons with respect to their responses to pharmacological agents as well as environmental and chemical toxins.

摘要

人类胚胎干细胞（hESCs）能够无限增殖，同时也能在体外分化，从而能够产生数量无限的正常人类神经元。在此，我们描述了一种使用源自hESCs的人类多巴胺能神经元进行体外神经毒性测定的方法。我们发现，能在人类身上引发帕金森病特征的多巴胺能神经毒素1-甲基-4-苯基吡啶鎓（MPP(+)），对源自hESCs的多巴胺能神经元具有毒性。用胶质细胞系衍生的神经营养因子进行处理，可保护酪氨酸羟化酶阳性神经元免受MPP(+)诱导的凋亡性细胞死亡、神经元突起丧失以及细胞内活性氧的形成。因此，源自hESCs的人类多巴胺能神经元的可得性，使得直接研究人类多巴胺能神经元在对药物制剂以及环境和化学毒素的反应方面的独特特征成为可能。