Highly efficient generation of human hepatocyte-like cells from induced pluripotent stem cells.
Highly efficient generation of human hepatocyte-like cells from induced pluripotent stem cells.
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DOI：
10.1002/hep.23354
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发表时间：
2010-01
期刊：
影响因子：
13.5
通讯作者：
Duncan, Stephen A.
中科院分区：
文献类型：
--
作者：
Si-Tayeb, Karim;Noto, Fallon K.;Nagaoka, Masato;Li, Jixuan;Battle, Michele A.;Duris, Christine;North, Paula E.;Dalton, Stephen;Duncan, Stephen A.
全世界范围内存在可用于正交肝移植（奥尔特）和肝细胞移植治疗的供体肝脏短缺。除了其治疗潜力外，原代人肝细胞还有助于研究人类肝脏疾病和发展的分子和遗传方面，并为药物毒性筛选和鉴定具有治疗多种代谢疾病潜力的新药提供平台。因此，对人肝细胞的需求远远超过其可用性。作为使用供体肝脏作为原代肝细胞来源的替代方案，我们探索了从诱导多能干细胞（iPS）细胞产生患者特异性人肝细胞的可能性。我们证明了小鼠iPS细胞保留了胎儿肝脏发育的全部潜力，并描述了一种程序，该程序有助于从iPS细胞有效生成高度分化的人肝细胞样细胞，该细胞显示关键的肝脏功能并可以整合到体内肝实质中。
There exists a worldwide shortage of donor livers available for orthotropic liver transplant (OLT) and hepatocyte transplantation therapies. In addition to their therapeutic potential, primary human hepatocytes facilitate the study of molecular and genetic aspects of human hepatic disease and development and provide a platform for drug toxicity screens and identification of novel pharmaceuticals with potential to treat a wide array of metabolic diseases. The demand for human hepatocytes, therefore, heavily outweighs their availability. As an alternative to using donor livers as a source of primary hepatocytes, we explored the possibility of generating patient specific human hepatocytes from induced pluripotent stem (iPS) cells. We demonstrate that mouse iPS cells retain full potential for fetal liver development and describe a procedure that facilitates the efficient generation of highly differentiated human hepatocyte–like cells from iPS cells that display key liver functions and can integrate into the hepatic parenchyma in vivo.
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