Rapid generation of mature hepatocyte-like cells from human induced pluripotent stem cells by an efficient three-step protocol

• DOI: 10.1002/hep.24790
• Publication Date: 2011-11-17T06:13:15Z
• Authors: Yu-Fan Chen; Chien-Yu Tseng; Hsei-Wei Wang; Hung-Chih Kuo; Vincent W. Yang; Oscar K. Lee
• Keywords: Pluripotent Stem Cells; 0301 basic medicine; Cell Transplantation; Hepatocyte Growth Factor; Gene Expression Profiling; Glutamine; Cell Differentiation; Mice, SCID; Oncostatin M; In Vitro Techniques; 3. Good health; Disease Models, Animal; Mice; 03 medical and health sciences; Treatment Outcome; Hepatocytes; Animals; Humans; Cell Lineage; Carbon Tetrachloride; Cells, Cultured; Liver Failure

Liver transplantation is the only definitive treatment for end-stage cirrhosis and fulminant liver failure, but lack of available donor livers a major obstacle to transplantation. Recently, induced pluripotent stem cells (iPSCs) derived from reprogramming somatic fibroblasts, have been shown resemble embryonic (ES) in that they properties potential differentiate into all cell lineages vitro, including hepatocytes. Thus, iPSCs could serve as favorable source wide range applications, drug toxicity testing, transplantation, patient-specific disease modeling. Here, we describe an efficient rapid three-step protocol able rapidly generate hepatocyte-like human iPSCs. This occurs because endodermal induction step allows more endoderm formation. We show hepatocyte growth factor (HGF), which synergizes with activin A Wnt3a, elevates expression marker Foxa2 (forkhead box a2) by 39.3% compared when HGF absent (14.2%) during step. In addition, iPSC-derived hepatocytes had similar gene profile mature Importantly, exhibited cytochrome P450 3A4 (CYP3A4) enzyme activity, secreted urea, uptake low-density lipoprotein (LDL), possessed ability store glycogen. Moreover, rescued lethal hepatic failure nonobese diabetic severe combined immunodeficient mouse model.We established differentiation functional may offer alternative option diseases.