Developing liver organoids from induced pluripotent stem cells (iPSCs): An alternative source of organoid generation for liver cancer research

Primary liver cancer (PLC) represents a significant proportion of all human cancers and constitutes a substantial health and economic burden to society. Traditional therapeutic approaches such as surgical resection and chemotherapy often fail due to tumour relapse or innate tumour chemoresistance. There is a dearth of efficient treatments for PLC in part due to the poor capacity of current laboratory models to reflect critical features of the native tumour in vivo. The increasing incorporation of organoid systems has led to a resurgence of interest in liver cancer research. Organoid systems show promise as the gold standard for recapitulating tumours in vitro. Further, developments in culturing techniques will improve the various shortcomings of the current systems. Induced pluripotent stem cell (iPSC)-derived liver organoids are a promising alternative to the conventional liver organoid model as it circumvents the need to rely on primary resections which are often scarce. In this concise review, we will discuss novel techniques for organoid culture with a focus on organoid co-cultures and their advantages over traditional organoid systems. A detailed technical protocol for the generation of iPSC-derived liver organoids is provided as an appendix.