Isolation of human induced pluripotent stem cell-derived dopaminergic progenitors by cell sorting for successful transplantation.
Isolation of human induced pluripotent stem cell-derived dopaminergic progenitors by cell sorting for successful transplantation.
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DOI：
10.1016/j.stemcr.2014.01.013
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发表时间：
2014-03-11
影响因子：
5.9
通讯作者：
Takahashi, Jun
中科院分区：
文献类型：
--
作者：
Doi, Daisuke;Samata, Bumpei;Katsukawa, Mitsuko;Kikuchi, Tetsuhiro;Morizane, Asuka;Ono, Yuichi;Sekiguchi, Kiyotoshi;Nakagawa, Masato;Parmar, Malin;Takahashi, Jun
人诱导多能干细胞（iPSCs）为帕金森病的细胞替代治疗提供了中脑多巴胺能（DA）神经元的重要来源。然而，ipsc来源的供体细胞不可避免地含有致瘤性或不合适的细胞。在这里，我们展示了人类ipsc衍生的DA祖细胞可以通过使用地板标记物CORIN进行细胞分选有效地分离。我们利用可扩展培养条件在人层粘连蛋白片段上诱导DA神经元，分选后的CORIN+细胞表达中脑DA祖细胞标记FOXA2和LMX1A。移植到6- ohda损伤大鼠体内后，CORIN+细胞存活并在体内分化为中脑DA神经元，运动行为明显改善，未形成肿瘤。特别是，处于NURR1+细胞优势期的CORIN+细胞表现出最好的存活和作为DA神经元的功能。我们的方法在可扩展性、安全性和效率方面是一种有利的策略，可能有利于临床应用。DA祖细胞通过CORIN+细胞的分选富集，可获得良好的DA神经元存活，而不形成肿瘤。NURR1+细胞优势期作为DA神经元表现出最佳的存活和功能。Takahashi和同事描述了一种从人类iPSCs中产生可移植的多巴胺能神经元用于临床应用的方案，并通过用CORIN分选的细胞在6- ohda损伤大鼠中存活良好，并作为中脑多巴胺能神经元发挥作用，肿瘤形成风险最小。
Human induced pluripotent stem cells (iPSCs) can provide a promising source of midbrain dopaminergic (DA) neurons for cell replacement therapy for Parkinson’s disease. However, iPSC-derived donor cells inevitably contain tumorigenic or inappropriate cells. Here, we show that human iPSC-derived DA progenitor cells can be efficiently isolated by cell sorting using a floor plate marker, CORIN. We induced DA neurons using scalable culture conditions on human laminin fragment, and the sorted CORIN+ cells expressed the midbrain DA progenitor markers, FOXA2 and LMX1A. When transplanted into 6-OHDA-lesioned rats, the CORIN+ cells survived and differentiated into midbrain DA neurons in vivo, resulting in significant improvement of the motor behavior, without tumor formation. In particular, the CORIN+ cells in a NURR1+ cell-dominant stage exhibited the best survival and function as DA neurons. Our method is a favorable strategy in terms of scalability, safety, and efficiency and may be advantageous for clinical application. DA neurons were highly efficiently induced from iPSCs on xeno-free laminin fragment DA progenitors were enriched by sorting of CORIN+ cells CORIN+ cell grafts resulted in good DA neuron survival without tumor formation NURR1+ cell-dominant stage exhibited the best survival and function as DA neurons Takahashi and colleagues have described a protocol for generating transplantable dopaminergic neurons from human iPSCs for clinical application and addressed that enriched dopaminergic progenitors by cell sorting with CORIN survived well and functioned as midbrain dopaminergic neurons in the 6-OHDA-lesioned rats and showed minimal risk of tumor formation.
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影响因子：
64.8
作者：
Kriks, Sonja;Shim, Jae-Won;Piao, Jinghua;Ganat, Yosif M.;Wakeman, Dustin R.;Xie, Zhong;Carrillo-Reid, Luis;Auyeung, Gordon;Antonacci, Chris;Buch, Amanda;Yang, Lichuan;Beal, M. Flint;Surmeier, D. James;Kordower, Jeffrey H.;Tabar, Viviane;Studer, Lorenz
通讯作者：
Studer, Lorenz
影响因子：
14.5
作者：
Mendez, I;Sanchez-Pernaute, R;Isacson, O
通讯作者：
Isacson, O
影响因子：
23.9
作者：
Fasano CA;Chambers SM;Lee G;Tomishima MJ;Studer L
通讯作者：
Studer L
DOI：
10.1007/978-1-61779-201-4_11
发表时间：
2011-01-01
期刊：
HUMAN PLURIPOTENT STEM CELLS: METHODS AND PROTOCOLS
影响因子：
--
作者：
Ausubel, Lara J.;Lopez, Patricia M.;Couture, Larry A.
通讯作者：
Couture, Larry A.
影响因子：
5.2
作者：
Brederlau, Anke;Correia, Ana Sofia;Li, Jia-Yi
通讯作者：
Li, Jia-Yi