The human hepatoma HepaRG cells: A highly differentiated model for studies of liver metabolism and toxicity of xenobiotics
The human hepatoma HepaRG cells: A highly differentiated model for studies of liver metabolism and toxicity of xenobiotics
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DOI：
10.1016/j.cbi.2006.12.003
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发表时间：
2007-05-20
影响因子：
5.1
通讯作者：
Guguen-Guillouzo, Christiane
中科院分区：
文献类型：
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作者：
Guillouzo, Andre;Corlu, Anne;Guguen-Guillouzo, Christiane
尽管原代人肝细胞有几个重要的局限性，但它仍然代表了异生物质代谢和毒性研究的体外金标准模型。由于各种肝脏特异性功能的丧失，特别是许多细胞色素P450（CYP）相关酶活性的丧失，阻止了来自肿瘤来源或通过致癌永生化获得的人肝细胞系的大量使用。我们在这里审查最近的结果获得了一个新的人肝癌细胞系，命名为HepaRG，来自人肝癌。这些细胞表现出独特的特征：当以低密度接种时，它们获得细长的未分化形态，积极分裂，并在达到汇合后形成典型的肝细胞样集落，周围环绕着胆管上皮样细胞。此外，与包括HepG2细胞在内的其他人肝癌细胞系相反，HepaRG细胞表达各种CYP（CYP 1A2、2B6、2C9、2E1、3A4）和核受体组成型雄烷受体（CAR）和雄烷X受体（PXR），其水平与培养的原代人肝细胞中发现的水平相当。它们还表达各种其他功能，如2相酶、顶端和小管ABC转运蛋白和基底外侧溶质载体转运蛋白、白蛋白、触珠蛋白以及作为成体肝细胞特异性标志物的醛缩酶B。HepaRG细胞可以代表原代人肝细胞的异源物质代谢和毒性研究的替代品，甚至更多，分析遗传毒性化合物的独特模型系统。(C)2007爱思唯尔爱尔兰有限公司保留所有权利。
Although they have several important limitations primary human hepatocytes still represent the in vitro gold standard model for xenobiotic metabolism and toxicity studies. The large use of human liver cell lines either from tumoral origin or obtained by oncogenic immortalisation is prevented by the loss of various liver-specific functions, especially many cytochrome P450 (CYP)-related enzyme activities. We review here recent results obtained with a new human hepatoma cell line, named HepaRG, derived from a human hepatocellular carcinoma. These cells exhibit unique features: when seeded at low density they acquire an elongated undifferentiated morphology, actively divided and after having reached confluency formed typical hepatocyte-like colonies surrounded by biliary epithelial-like cells. Moreover contrary to other human hepatoma cell lines including HepG2 cells, HepaRG cells express various CYPs (CYP1A2, 2B6, 2C9, 2E1, 3A4) and the nuclear receptors constitutive androstane receptor (CAR) and pregnane X receptor (PXR) at levels comparable to those found in cultured primary human hepatocytes. They also express various other functions such phase 2 enzymes, apical and canalicular ABC transporters and basolateral solute carrier transporters, albumin, haptoglobin as well as aldolase B that is a specific marker of adult hepatocytes. HepaRG cells could represent a surrogate to primary human hepatocytes for xenobiotic metabolism and toxicity studies and even more, a unique model system for analysing genotoxic compounds. (C) 2007 Elsevier Ireland Ltd. All rights reserved.