Using liver models generated from human-induced pluripotent stem cells (iPSCs) for evaluating chemical-induced modifications and disease across liver developmental stages.

The liver is a pivotal organ regulating critical developmental stages of fetal metabolism and detoxification. Though numerous studies have evaluated links between prenatal/perinatal exposures and adverse health outcomes in the developing fetus, the central role of liver to health disruptions resulting from these exposures remains understudied, especially concerning early development and later-in-life health outcomes. While numerous in vitro methods for evaluating liver toxicity have been established, the use of iPSC-derived hepatocytes appears to be particularly well suited to contribute to this critical research gap due to their potential to model a diverse range of disease phenotypes and different stages of liver development. The following key aspects are reviewed: (1) an introduction to developmental liver toxicity; (2) an introduction to embryonic and induced pluripotent stem cell models; (3) methods and challenges for deriving liver cells from stem cells; and (4) applications for iPSC-derived hepatocytes to evaluate liver developmental stages and their associated responses to insults. We conclude that iPSC-derived hepatocytes have great potential for informing liver toxicity and underlying disease mechanisms via the generation of patient-specific iPSCs; implementing large-scale drug and chemical screening; evaluating general biological responses as a potential surrogate target cell; and evaluating inter-individual disease susceptibility and response variability.