Multistage Hepatic Differentiation from Human Induced Pluripotent Stem Cells

Efficient hepatic differentiation technologies designed for patient specific induced pluripotent stem (iPS) cells may provide an unlimited hepatocyte source which can be utilized in drug screening, disease modeling, and cell therapy. This chapter describes the methods we use to differentiate human iPS cells into functional hepatic cells. Our hepatic differentiation protocol has been applicable for many human iPS cell types of various sources and conditions (i.e., iPS cells derived from healthy donor or patients, as well as iPS cells generated using virus free or viral methods). The protocol is composed of three stages: definitive endoderm induction, hepatic progenitor induction and expansion, and hepatocyte maturation. We also describe the protocols for detecting iPS cell-derived functional hepatocytes both in vitro and in vivo.