title: Hepatic differentiation of embryonic stem cells by murine fetal liver mesenchymal cells.
abstract: Hepatocytes derived from embryonic stem cells (ESCs) are a potential cell source for regenerative medicine. However, it has been technically difficult to differentiate ESCs into mature hepatocytes because the definitive growth factors and molecular mechanisms governing hepatocyte differentiation have not yet been well defined. The CD45(-)CD49f(+/-)Thy1(+)gp38(+) mesenchymal cells that reside in murine fetal livers induce hepatic progenitor cells to differentiate into mature hepatocytes by direct cell-cell contact. Utilizing these cells, we employ a two-step procedure for hepatic maturation of ESCs: first, ESCs are differentiated into endodermal cells or hepatic progenitor cells, and second, ESC-derived endodermal cells are matured into functional hepatocytes by coculture with murine fetal liver mesenchymal cells. The ESC-derived hepatocyte-like cells possess hepatic functions, including ammonia removal activity, albumin secretion ability, glycogen synthesis and storage, and cytochrome P450 enzymatic activity.
authors.affiliation: Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan. taishii@kuhp.kyoto-u.ac.jp
authors.forename: Takamichi
authors.initials: T
authors.lastname: Ishii
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yasuchika
authors.forename: Iwao
authors.initials: I
authors.lastname: Ikai
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects; D004707:Endoderm / Q000166:cytology; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D061252:Feeder Cells / Q000166:cytology; D005333:Fetus / Q000166:cytology*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D039503:Integrin alpha6 / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008099:Liver / Q000166:cytology* / Q000196:embryology*; D008562:Membrane Glycoproteins / Q000378:metabolism; D008648:Mesoderm / Q000166:cytology*; D051379:Mice; D018800:Thy-1 Antigens / Q000378:metabolism; D000098853:Podoplanin
chemical_list: D016222:Fibroblast Growth Factor 2; D017228:Hepatocyte Growth Factor; D039503:Integrin alpha6; D017493:Leukocyte Common Antigens; D008562:Membrane Glycoproteins; D018800:Thy-1 Antigens; C490441:Pdpn protein, mouse; D000098853:Podoplanin