title: Reversal of mouse hepatic failure using an implanted liver-assist device containing ES cell-derived hepatocytes.
abstract: Severe acute liver failure, even when transient, must be treated by transplantation and lifelong immune suppression. Treatment could be improved by bioartificial liver (BAL) support, but this approach is hindered by a shortage of human hepatocytes. To generate an alternative source of cells for BAL support, we differentiated mouse embryonic stem (ES) cells into hepatocytes by coculture with a combination of human liver nonparenchymal cell lines and fibroblast growth factor-2, human activin-A and hepatocyte growth factor. Functional hepatocytes were isolated using albumin promoter-based cell sorting. ES cell-derived hepatocytes expressed liver-specific genes, secreted albumin and metabolized ammonia, lidocaine and diazepam. Treatment of 90% hepatectomized mice with a subcutaneously implanted BAL seeded with ES cell-derived hepatocytes or primary hepatocytes improved liver function and prolonged survival, whereas treatment with a BAL seeded with control cells did not. After functioning in the BAL, ES cell-derived hepatocytes developed characteristics nearly identical to those of primary hepatocytes.
authors.affiliation: Department of Surgery, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Soto-Gutiérrez
authors.forename: Naoya
authors.initials: N
authors.lastname: Kobayashi
authors.forename: Jorge David
authors.initials: JD
authors.lastname: Rivas-Carrillo
authors.forename: Nalu
authors.initials: N
authors.lastname: Navarro-Alvarez
authors.forename: Debiao
authors.initials: D
authors.lastname: Zhao
authors.forename: Debaio
authors.initials: D
authors.lastname: Zhao
authors.forename: Teru
authors.initials: T
authors.lastname: Okitsu
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Noguchi
authors.forename: Hesham
authors.initials: H
authors.lastname: Basma
authors.forename: Yashuhiko
authors.initials: Y
authors.lastname: Tabata
authors.forename: Yong
authors.initials: Y
authors.lastname: Chen
authors.forename: Kimiaki
authors.initials: K
authors.lastname: Tanaka
authors.forename: Michiki
authors.initials: M
authors.lastname: Narushima
authors.forename: Atsushi
authors.initials: A
authors.lastname: Miki
authors.forename: Tadayoshi
authors.initials: T
authors.lastname: Ueda
authors.forename: Hee-Sook
authors.initials: HS
authors.lastname: Jun
authors.forename: Ji-Won
authors.initials: JW
authors.lastname: Yoon
authors.forename: Jane
authors.initials: J
authors.lastname: Lebkowski
authors.forename: Noriaki
authors.initials: N
authors.lastname: Tanaka
authors.forename: Ira J
authors.initials: IJ
authors.lastname: Fox
mesh_terms: D028341:Activins / Q000502:physiology; D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods; D002454:Cell Differentiation / Q000502:physiology*; D017690:Cell Transplantation / Q000379:methods / Q000502:physiology*; D053595:Embryonic Stem Cells / Q000502:physiology* / Q000637:transplantation*; D016222:Fibroblast Growth Factor 2 / Q000502:physiology; D017228:Hepatocyte Growth Factor / Q000502:physiology; D022781:Hepatocytes / Q000166:cytology / Q000502:physiology*; D006801:Humans; D017114:Liver Failure, Acute / Q000628:therapy*; D019164:Liver, Artificial; D051379:Mice; D023421:Models, Animal
chemical_list: C422405:activin A; D016222:Fibroblast Growth Factor 2; D028341:Activins; D017228:Hepatocyte Growth Factor