The Use of iPSC-Derived Liver Organoids as an Exclusive Toxicity Testing Tool

Abstract

Drug-induced liver injury (DILI) remains a primary reason for drug withdrawal from the market, often after large amounts of money have been invested and patients put at risk in clinical trials. In dealing with DILI, the current 2D models are not sufficient in predicting DILI, thereby resulting in DILI discovered in clinical trials and postmarket surveillance. In recent decades, organoid technology has gained much attention and interest. The self-organizing and self-renewing features of organoids has led to their application in disease modeling, regenerative and personalized medicine, as well as in toxicity testing. The emergence of organoid technology challenges current in vitro and in vivo toxicity testing models as it overcomes several drawbacks two dimensional (2D) traditional models face. This review discusses the use of induced human pluripotent stem cells (iPSC) to make liver organoids specifically. Among many sources to make liver organoids, iPSCs are the least invasive and can ensure reproducible productions of liver organoids which better recapitulates the human liver in vivo. This paper, in particular, looks at the potential of iPSC-derived liver organoids as an exclusive tool for liver toxicity testing, including liver organoid construction, functionality, hepatic biomarkers measured, commercial availability, and challenges.