Author:
Xu Jiecheng,Pan Daogang,Liao Wei,Jia Zhidong,Pan Mingxin,Weng Jun,Han Xu,Li Shao,Li Yang,Liang Kangyan,Zhou Shuqin,Peng Qing,Gao Yi
Abstract
Background: Drug-induced liver injury is one of the main reasons of withdrawals of drugs in postmarketing stages. However, an experimental model(s) which can accurately recapitulates liver functions and reflects the level of drug hepatotoxicity is lack. In this study, we assessed drug hepatotoxicity using a novel three-dimensional hepatic plate-like hydrogel fiber (3D-P) co-culture system.Methods: During the 28-days culture period, the liver-specific functions, hepatocyte polarity, sensitivity of drug-induced toxicity of 3D-P co-culture system were evaluated with 2D co-culture, collagen sandwich co-culture, 3D hybrid hydrogel fiber co-culture and human primary hepatocytes as controls. High-content imaging and analysis (HCA) methods were used to explore the hepatotoxicity mechanism of five statins.Results: The 3D-P co-culture system showed enhancing liver-specific functions, cytochrome P450 enzymes (CYPs) metabolic activity and bile excretion, which were considered to result from improved hepatocyte polarity. Three of the statins may cause acute or chronic hepatotoxicity by via different mechanisms, such as cholestatic liver injury.Conclusion: Our 3D-P co-culture system is characterized by its biomimetic hepatic plate-like structure, long-term stable liver specificity, and prominent bile secretion function, making it applicable for acute/chronic drug hepatotoxicity assessments.
Funder
National Key Research and Development Program of China
National Natural Science Foundation of China
Natural Science Foundation of Guangdong Province
Subject
Biomedical Engineering,Histology,Bioengineering,Biotechnology
Cited by
5 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献