In Vitro Modeling of Alcohol-Induced Liver Injury Using Human-Induced Pluripotent Stem Cells.
In Vitro Modeling of Alcohol-Induced Liver Injury Using Human-Induced Pluripotent Stem Cells.
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DOI：
10.1007/7651_2014_168
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Jang YY
中科院分区：
文献类型：
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作者：
Tian L;Prasad N;Jang YY
长期以来，人们一直认为饮酒与大多数肝脏疾病有关，并已发现酒精会影响胎儿和成人的肝功能。尽管酒精性肝病是世界上发病率和死亡率的主要原因之一，但由于缺乏与人类相关的研究模型，目前还没有有效的预防或治疗酒精性肝病的策略。最近成功地从人诱导多能细胞（iPSCs）中生成功能活跃的成熟肝细胞样细胞，使我们能够更好地了解酒精对肝功能的影响。在这里，我们描述了酒精暴露对人类多能干细胞衍生的多阶段肝细胞类型的方法和影响，试图概括与ALD相关的肝组织损伤的早期阶段。我们将ipsc诱导的不同阶段的肝细胞暴露于病理生理浓度的乙醇中。除了阶段特异性分子标记外，我们还测量了肝细胞损伤的几个关键细胞参数，包括凋亡、增殖和脂质积累。
Alcohol consumption has long been associated with a majority of liver diseases and has been found to influence both fetal and adult liver functions. In spite of being one of the major causes of morbidity and mortality in the world, currently, there are no effective strategies that can prevent or treat alcoholic liver disease (ALD), due to a lack of human-relevant research models. Recent success in generation of functionally active mature hepatocyte-like cells from human-induced pluripotent cells (iPSCs) enables us to better understand the effects of alcohol on liver functions. Here, we describe the method and effect of alcohol exposure on multistage hepatic cell types derived from human iPSCs, in an attempt to recapitulate the early stages of liver tissue injury associated with ALD. We exposed different stages of iPSC-induced hepatic cells to ethanol at a pathophysiological concentration. In addition to stage-specific molecular markers, we measured several key cellular parameters of hepatocyte injury, including apoptosis, proliferation, and lipid accumulation.