Isolation and transplantation of dopaminergic neurons generated from mouse embryonic stem cells
Isolation and transplantation of dopaminergic neurons generated from mouse embryonic stem cells
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DOI：
10.1016/j.neulet.2004.03.074
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发表时间：
2004-06-03
影响因子：
2.5
通讯作者：
Okano, H
中科院分区：
文献类型：
--
作者：
Yoshizaki, T;Inaji, M;Okano, H
胚胎干细胞（ES）与PA6基质细胞共培养时可分化为产生多巴胺（DA）的神经元，但所产生的培养物含有多种未知细胞。为了标记混合群体中的活DA神经元，我们将酪氨酸羟化酶（TH）基因启动子控制的GFP报告基因导入ES细胞。从携带TH-GFPreporter基因的ES细胞分化出来的th免疫反应细胞中观察到GFP的表达。对GFP荧光细胞进行荧光活化细胞分选，从混合细胞群中对表达GFP的DA神经元进行分选，并将分选后的GFP（+）细胞移植到帕金森病大鼠模型中。这些细胞中的一些存活下来并支配宿主纹状体，导致帕金森行为缺陷的部分恢复。这种es细胞来源的DA神经元的分离和移植策略将有助于DA神经元的细胞和分子研究以及在帕金森病治疗中的临床应用。2004爱思唯尔爱尔兰有限公司版权所有。
Embryonic stem (ES) cells differentiate into dopamine (DA)-producing neurons when co-cultured with PA6 stromal cells, but the resulting cultures contain a variety of unidentified cells. In order to label live DA neurons in mixed populations, we introduced a GFP reporter under the control of the tyrosine hydroxylase (TH) gene promoter into ES cells. GFP expression was observed in TH-immunoreactive cells that differentiated from the ES cells that carried the TH-GFPreporter gene. DA neurons expressing GFP were sorted from the mixed cell population by fluorescence-activated cell sorting of cells exhibiting GFP fluorescence, and the sorted GFP(+) cells obtained were transplanted into a rat model of Parkinson's disease. Some of these cells survived and innervated the host striatum, resulting in a partial recovery from parkinsonian behavioral defects. This strategy of isolation and transplantation of ES-cell-derived DA neurons should be useful for cellular and molecular studies of DA neurons and for clinical application in the treatment of Parkinson's disease. (C) 2004 Elsevier Ireland Ltd. All rights reserved.