Differentiation of human induced pluripotent stem cells to hepatocyte-like cells for toxicological applications: recent advances using small molecule approaches

Abstract Hepatocytes play a central role in toxicological studies, yet the paucity and variability in supply and instability under in vitro conditions limit the use of primary human hepatocytes in such applications. In the last decade, there has been burgeoning interest in the differentiation of human induced pluripotent stem cells (iPSCs) to hepatocyte-like cells (HLCs) as a defined and renewable source of hepatic cells. Many protocols have been developed thus far, which generated cells with encouraging results in terms of marker expression and functional assays. However, most of these methods rely on the use of growth factors therefore suffering the disadvantages of high cost and low reproducibility. Recently, increasing studies have shown the feasibility and advantages of using small molecules (SMs) for the generation of HLCs. In this chapter, we present a historical overview and current status on the differentiation of iPSCs into HLCs, and focus on recent development of SM-based differentiation protocols. We also discuss applications of HLCs in hepatotoxicity studies and offer some perspectives on future development of the field.