title: High efficient differentiation of functional hepatocytes from porcine induced pluripotent stem cells.
abstract: Hepatocyte transplantation is considered to be a promising therapy for patients with liver diseases. Induced pluripotent stem cells (iPSCs) provide an unlimited source for the generation of functional hepatocytes. In this study, we generated iPSCs from porcine ear fibroblasts (PEFs) by overexpressing Sox2, Klf4, Oct4, and c-Myc (SKOM), and developed a novel strategy for the efficient differentiation of hepatocyte-like cells from porcine iPSCs by following the processes of early liver development. The differentiated cells displayed the phenotypes of hepatocytes, exhibited classic hepatocyte-associated bio-functions, such as LDL uptake, glycogen storage and urea secretion, as well as possessed the metabolic activities of cytochrome P-450 (CYP) 3A and 2C. Furthermore, we compared the hepatocyte differentiation efficacy of our protocol with another published method, and the results demonstrated that our differentiation strategy could significantly improve the generation of morphological and functional hepatocyte-like cells from porcine iPSCs. In conclusion, this study establishes an efficient method for in vitro generation of functional hepatocytes from porcine iPSCs, which could represent a promising cell source for preclinical testing of cell-based therapeutics for liver failure and for pharmacological applications.
authors.affiliation: Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan, Hubei, China; Department of Developmental Biology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Ying
authors.initials: Y
authors.lastname: Ao
authors.affiliation: Department of Developmental Biology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Jocelyn Danielle
authors.initials: JD
authors.lastname: Mich-Basso
authors.affiliation: Department of Developmental Biology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Bo
authors.initials: B
authors.lastname: Lin
authors.affiliation: Department of Developmental Biology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
mesh_terms: D000818:Animals; D065150:Cellular Reprogramming; D005347:Fibroblasts / Q000166:cytology; D020869:Gene Expression Profiling; D005822:Genetic Vectors / Q000235:genetics; D022781:Hepatocytes / Q000166:cytology* / Q000378:metabolism; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D016086:Lentivirus / Q000235:genetics; D008099:Liver / Q000166:cytology / Q000254:growth & development; D008297:Male; D009928:Organ Specificity; D013552:Swine