Progress of Hepatocyte-like Cell Models in the Research of Hepatic Metabolism and Toxicity of Drugs

Drug-induced liver injury (DILI) is a major cause of clinical trial failure and drug attrition. Before a clinical trial, humanized hepatocyte-like cell models are usually used for assessment of drug metabolism and prediction of potential DILI risk. Currently, the commonly used hepatocyte models include hepatoma cell lines, immortalized primary hepatocytes, stem cell-derived hepatocytes and directly-induced hepatocyte-like cells. However, all these hepatocyte models could not fully recapitulate the function of hepatocytes in vivo. Various in vitro hepatocyte culture systems have been developed to culture in vitro hepatocyte models as mimetics of hepatocytes in liver. Compared to 2D and sandwich culture models, 3D culture models and microchips can better simulate the in vivo microenvironment of hepatocytes, serving as the best models of hepatocyte in terms of morphology and function. The advances of hepatocyte-like cell models in the study of hepatic metabolism and toxicity of drugs have been reviewed in this paper, providing reference for appropriate selection of hepatocyte-like cell models in the preclinical studies of drugs.