Self-renewing endodermal progenitor lines generated from human pluripotent stem cells.
Self-renewing endodermal progenitor lines generated from human pluripotent stem cells.
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DOI：
10.1016/j.stem.2012.02.024
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发表时间：
2012-04-06
期刊：
影响因子：
23.9
通讯作者：
Gadue, Paul
中科院分区：
文献类型：
--
作者：
Cheng, Xin;Ying, Lei;Lu, Lin;Galvao, Aline M.;Mills, Jason A.;Lin, Henry C.;Kotton, Darrell N.;Shen, Steven S.;Nostro, M. Cristina;Choi, John Kim;Weiss, Mitchell J.;French, Deborah L.;Gadue, Paul
人类多能干细胞在实验室研究和基于细胞的治疗中的应用受到其肿瘤形成潜力和在体外产生纯分化细胞类型群的能力有限的阻碍。为了解决这些问题，我们从人类胚胎干细胞和诱导多能干细胞中建立了内胚层祖细胞系（EP）。建立了优化的生长条件，允许近乎无限（>1016）的 EP 细胞自我更新，其中它们表现出定形内胚层的形态和基因表达模式特征。在体外操纵其培养条件或移植到小鼠体内后，克隆衍生的 EP 细胞分化成多种内胚层谱系，包括单激素葡萄糖反应性胰腺 β 细胞、肝细胞和肠上皮细胞。重要的是，EP 细胞在体内不致瘤。因此，EP细胞代表了研究内胚层规格的强大工具，并为移植治疗提供了潜在安全的内胚层衍生组织来源。
The use of human pluripotent stem cells for laboratory studies and cell-based therapies is hampered by their tumor-forming potential and limited ability to generate pure populations of differentiated cell types in vitro. To address these issues, we established endodermal progenitor (EP) cell lines from human embryonic and induced pluripotent stem cells. Optimized growth conditions were established that allow near unlimited (>1016) EP cell self-renewal in which they display a morphology and gene expression pattern characteristic of definitive endoderm. Upon manipulation of their culture conditions in vitro or transplantation into mice, clonally derived EP cells differentiate into numerous endodermal lineages, including monohormonal glucose-responsive pancreatic β-cells, hepatocytes, and intestinal epithelia. Importantly, EP cells are nontumorigenic in vivo. Thus, EP cells represent a powerful tool to study endoderm specification and offer a potentially safe source of endodermal-derived tissues for transplantation therapies.
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