Human induced pluripotent stem cells (iPSCs) are thought to have the potential to revolutionize research and therapy of liver diseases by providing a source of hepatocytes for autologous cell therapy and disease modeling. Progress has been made in advancing the differentiation of iPSCs into hepatocytes (iPSC-Heps) in vitro (see, e.g., Si-Tayeb et al., HEPATOLOGY 51: 297-305 (2010); Rashid et al., J CLIN INVEST 120: 3127-3136 (2010); Ma et al., STEM CELLS TRANSL MED (2013)). However, cells that replicate the ability of human primary adult hepatocytes (aHeps) to proliferate extensively in vivo have not been reported. This deficiency has not only hampered efforts to recreate human liver diseases in mice, it has also cast doubt on the potential of iPSC-Heps for liver cell therapy. Significant problems remain that include the need for extensive post-transplant expansion to establish and sustain a therapeutically effective liver cell mass in patients, a lesson learned from clinical trials of adult hepatocyte transplantation (see, e.g., Puppi et al., CELL TRANSPLANT 21: 1-10 (2012)).