In vitro models for liver toxicity testing.
In vitro models for liver toxicity testing.
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DOI：
10.1039/c2tx20051a
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发表时间：
2013-01-01
影响因子：
2.1
通讯作者：
Rusyn I
中科院分区：
文献类型：
--
作者：
Soldatow VY;Lecluyse EL;Griffith LG;Rusyn I
多年来，已经开发了各种肝脏来源的体外模型系统，以能够研究化学品和药物的潜在副作用。肝组织切片、分离的微粒体、灌注肝脏、永生化细胞系和原代肝细胞已被广泛使用。永生化细胞系和原代分离肝细胞是目前最广泛用于肝毒性测试的体外模型。有限的通量、活力丧失以及肝脏特异性功能和基因表达的降低是这些模型的常见缺点。体外肝毒性领域的最新进展包括三维组织构建体和生物人工肝、各种细胞类型与肝细胞的共培养以及干细胞分化为肝谱系样细胞。为了给培养的肝细胞提供更加生理化的环境，一些新型细胞培养系统结合了流体流动、微循环和其他形式的器官型微环境。共培养的目的是保留肝脏特异性的形态和功能，超越纯实质细胞培养物提供的形态和功能。胚胎和成人组织来源的干细胞可以提供来自多个个体的肝细胞的无限供应，以提高再现性并能够测试个体特异性毒性。这篇综述描述了各种传统和新颖的体外肝脏模型，并提供了对每个测试系统所带来的挑战和机遇的看法。
Over the years, various liver-derived in vitro model systems have been developed to enable investigation of the potential adverse effects of chemicals and drugs. Liver tissue slices, isolated microsomes, perfused liver, immortalized cell lines, and primary hepatocytes have been used extensively. Immortalized cell lines and primary isolated liver cells are currently most widely used in vitro models for liver toxicity testing. Limited throughput, loss of viability, and decreases in liver-specific functionality and gene expression are common shortcomings of these models. Recent developments in the field of in vitro hepatotoxicity include three-dimensional tissue constructs and bioartificial livers, co-cultures of various cell types with hepatocytes, and differentiation of stem cells into hepatic lineage-like cells. In an attempt to provide a more physiological environment for cultured liver cells, some of the novel cell culture systems incorporate fluid flow, micro-circulation, and other forms of organotypic microenvironments. Co-cultures aim to preserve liver-specific morphology and functionality beyond those provided by cultures of pure parenchymal cells. Stem cells, both embryonic- and adult tissue-derived, may provide a limitless supply of hepatocytes from multiple individuals to improve reproducibility and enable testing of the individual-specific toxicity. This review describes various traditional and novel in vitro liver models and provides a perspective on the challenges and opportunities afforded by each individual test system.