title: [Robust differentiation of fetal hepatocytes from human embryonic stem cells and iPS].
abstract: Hepatocyte transplantation is considered as an alternative to organ transplantation in particular for the treatment of liver metabolic diseases. However, due to the difficulties to obtain a large number of hepatocytes, new sources of cells are needed. These cells could be either of hepatic origin (hepatic stem cells) or extrahepatic such as mesenchymal stem cells or pluripotent stem cells (human embryonic stem cells [hESC] or iPS). We developed a new method to differentiate hESCs into fetal hepatocytes. These conditions recapitulate the main liver developmental stages, using fully defined medium devoid of animal products or unknown factors. The differentiated cells express many fetal hepatocytes markers (cytochrome P450 3A7, albumin, alpha-1-antitrypsin, etc.). The cells display specific hepatic functions (ammonia metabolism, excretion of indocyanin green) and are capable to engraft and express hepatic proteins two months after transplantation into newborn uPAxrag2gc-/- mouse liver. We have also showed that this approach is transposable to human iPS, and further studies on animal models will allow us to compare the in vivo potential of these two sources of pluripotent cells. Finally, only studies on large animals such as nonhuman primates will validate an eventual clinical application.
authors.affiliation: Inserm U972, IFR 93, Hôpital du Kremlin-Bicêtre, 78, rue du Général Leclerc, 94270 Le Kremlin-Bicêtre, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Touboul
authors.forename: Ludovic
authors.initials: L
authors.lastname: Vallier
authors.forename: Anne
authors.initials: A
authors.lastname: Weber
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers; D002454:Cell Differentiation; D019070:Cell Lineage; D054338:Cell Transdifferentiation; D002478:Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000637:transplantation; D003470:Culture Media / Q000494:pharmacology; D004064:Digestive System / Q000196:embryology; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects; D004707:Endoderm / Q000166:cytology; D018507:Gene Expression Regulation, Developmental; D022781:Hepatocytes / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation; D006801:Humans; D008099:Liver / Q000166:cytology / Q000196:embryology; D051379:Mice; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000637:transplantation; D014183:Transplantation, Heterologous
chemical_list: D015415:Biomarkers; D003470:Culture Media