Advances in generating liver cells from pluripotent stem cells as a tool for modeling liver diseases

Developing robust in vitro models of the liver is essential for studying the pathogenesis of liver diseases, hepatotoxicity testing, and regenerative medicine. Earlier studies were conducted using cell lines derived from hepatomas. Due to the inherent limitations of cell lines, researchers used primary human hepatocytes (PHHs), which are considered a gold standard for in vitro modeling of the liver. However, due to the high cost of PHHs and lack of donors, researchers have sought an alternative source for functional liver cells. Pluripotent stem cells (PSCs) emerged as a viable alternative due to their plasticity and high proliferative capacity. This review gives an overview of the major advances that have been achieved to develop protocols to generate liver cells such as hepatocytes, cholangiocytes, and Küpffer cells from PSCs. We also discuss their application in modeling the pathogenesis of liver diseases such as drug-induced liver injury, acute liver failure, and hepatic steatosis.