Human liver spheroids in chemically defined conditions for studies of gene-drug, drug-drug and disease-drug interactions.

Abstract

Recent phenotypically and functionally relevant human hepatic in vitro systems combine the ability to preserve interindividual molecular differences between patients' livers in culture with the accessibility and high-throughput compatibility of in vitro assays. These features facilitate studies of specific genetic polymorphisms by using cells from donors with defined variants of interest or by selective gene knock-down experiments. Furthermore, these models constitute promising tools to evaluate drug-drug interactionsas well as the effects of liver diseases on drug pharmacokinetics in co-cultures of hepatocytes and non-parenchymal cells. In the near future, we anticipate that these tools will be of high relevance for predicting the in vivo kinetics, toxicity and drug-drug interactions of drug candidates already during preclinical development.