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

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.