基于3D体外培养模型的化学物质肝毒性预测研究进展
Advances in Predicting Hepatotoxicity of Chemicals based on 3D in vitro Culture Models
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摘要: 精准预测化学物质肝毒性对保护人类生命健康安全具有重要意义。为了避免动物实验固有的物种间差异性和局限性，开发和利用与人源肝脏生理功能直接相关的体外模型至关重要。三维(3D)体外细胞培养模型相比于二维(2D)模型能更好地保留肝细胞代谢功能，再现肝脏内多种细胞相互作用的复杂环境，是体外模拟肝脏生理功能的一大进步，并初步在药物毒性评估方面获得应用的同时，也被引入到环境毒理学领域用于预测环境化学物质的肝毒性。本文介绍了目前常用3D体外细胞培养模型的制备方法，综述了其在环境化学物质(纳米材料、持久性有机污染物和新型有机污染物等)肝毒性预测方面的应用现状，最后探讨了3D肝细胞体外培养模型在有害结局路径指导下开展肝毒性预测的研究与应用前景。Abstract: Prediction and prevention of chemicals-induced hepatotoxicity is one of the most important aspects to protect human health. To enhance the prediction of human hepatotoxicity from chemical hazards, various in vitro approaches have been developed. One of the major challenges was to enhance the human physiological relevance of hepatic in vitro systems. Three-dimensional (3D) hepatocyte culture models allow better preservation of hepatocyte metabolic functions for a relatively long period culture than that of 2D models and recapitulate multi-cellular interactions, which represent a major advancement in mimicking liver physiological functions by in vitro models. 3D hepatocyte culture models have been rapidly developed and introduced into environmental field for predicting hepatotoxicity of environmental chemicals. This paper reviews the methods for generating 3D hepatocyte in vitro culture models, as well as the application of these models in hepatotoxicity prediction of environmental chemicals, such as nanomaterials, persistent organic pollutants, emerging organic pollutants, etc. Finally, future research opportunities have also been discussed on how to use 3D in vitro culture models for more accurately predicting hepatotoxicity of environmental chemicals under the guidance of adverse outcome pathways (AOPs).
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