Guguen-Guillouzo Christiane, Guillouzo Andre
INSERM U522, Régulation des équilibres fonctionnels du foie normal et pathologique, Hopital Pontchaillou, Rennes, France.
Methods Mol Biol. 2010;640:1-40. doi: 10.1007/978-1-60761-688-7_1.
In vitro hepatocyte models represent very useful systems in both fundamental research and various application areas. Primary hepatocytes appear as the closest model for the liver in vivo. However, they are phenotypically unstable, have a limited life span and in addition, exhibit large interdonor variability when of human origin. Hepatoma cell lines appear as an alternative but only the HepaRG cell line exhibits various functions, including major cytochrome P450 activities, at levels close to those found in primary hepatocytes. In vitro hepatocyte models have brought a substantial contribution to the understanding of the biochemistry, physiology, and cell biology of the normal and diseased liver and in various application domains such as xenobiotic metabolism and toxicity, virology, parasitology, and more generally cell therapies. In the future, new well-differentiated hepatocyte cell lines derived from tumors or from either embryonic or adult stem cells might be expected and although hepatocytes will continue to be used in various fields, these in vitro liver models should allow marked advances, especially in cell-based therapies and predictive and mechanistic hepatotoxicity of new drugs and other chemicals. All models will benefit from new developments in throughput screening based on cell chips coupled with high-content imaging and in toxicogenomics technologies.
体外肝细胞模型在基础研究和各个应用领域都是非常有用的系统。原代肝细胞似乎是最接近体内肝脏的模型。然而，它们在表型上不稳定，寿命有限，此外，来源于人类时，供体间差异很大。肝癌细胞系是一种替代选择，但只有HepaRG细胞系表现出多种功能，包括主要的细胞色素P450活性，其水平与原代肝细胞中的水平相近。体外肝细胞模型为理解正常和患病肝脏的生物化学、生理学和细胞生物学以及在各种应用领域，如异生物质代谢和毒性、病毒学、寄生虫学以及更广泛的细胞治疗，做出了重大贡献。未来，有望获得源自肿瘤或胚胎或成体干细胞的新的高度分化的肝细胞系，尽管肝细胞将继续在各个领域使用，但这些体外肝脏模型应能带来显著进展，特别是在基于细胞的治疗以及新药和其他化学品的预测性和机制性肝毒性方面。所有模型都将受益于基于细胞芯片结合高内涵成像的高通量筛选以及毒理基因组学技术的新发展。
