Abstract：
Variability in supply, paucity of donors and cellular instability under in vitro conditions have limited the application of primary human hepatocytes (PHHs) to hepatotoxicity testing. Therefore, alternative sources have been sought for functional liver cells. Many of the earlier in vitro hepatotoxicity studies were carried out using hepatoma-derived cell lines. These cell lines have overcome some of the limitations of PHHs with regard to phenotypic stability and availability; however, they suffer from their own inherent limitations, such as the lack of drug-metabolizing functionality, which renders them inadequate for situations where toxic metabolite formation of the parent drug occurs. In the last decade we have witnessed a burgeoning interest of the research community in using hepatocyte-like cells (HLCs) derived from human induced pluripotent stem cells (iPSCs) as in vitro hepatotoxicity models. HLCs offer the perspective of a defined and renewable supply of functional hepatocytes; more importantly, HLCs maintain their original donor genotype and afford donor diversity, thus opening new avenues to patient-specific toxicity testing. In this review, we first introduce various in vitro hepatotoxicity models, then focus on HLCs and their application in hepatotoxicity studies, and finally offer some perspectives on future developments of the field.
摘要：
供应的可变性，供体的缺乏和体外条件下的细胞不稳定性限制了原代人肝细胞（PHHs）在肝毒性测试中的应用。因此,已经寻找功能性肝细胞的替代来源。许多早期的体外肝毒性研究是使用肝癌衍生的细胞系进行的。这些细胞系已经克服了PHHs在表型稳定性和可用性方面的一些局限性；然而，他们有自己固有的局限性，例如缺乏药物代谢功能，这使得它们不足以用于发生母体药物的毒性代谢物形成的情况。在过去的十年中，我们目睹了研究界对使用源自人类诱导多能干细胞（iPSC）的肝细胞样细胞（HLC）作为体外肝毒性模型的兴趣。HLCs提供功能肝细胞的定义和可再生供应的观点;更重要的是，HLCs保持其原始供体基因型并提供供体多样性，从而为患者特异性毒性测试开辟了新的途径。在这次审查中,我们首先介绍各种体外肝毒性模型，然后重点关注HLC及其在肝毒性研究中的应用，最后对该领域的未来发展提出了一些看法。
