PMID- 17086173 OWN - NLM STAT- MEDLINE DCOM- 20061228 LR - 20220311 IS - 1087-0156 (Print) IS - 1087-0156 (Linking) VI - 24 IP - 11 DP - 2006 Nov TI - Reversal of mouse hepatic failure using an implanted liver-assist device containing ES cell-derived hepatocytes. PG - 1412-9 AB - 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. FAU - Soto-Gutierrez, Alejandro AU - Soto-Gutierrez A AD - Department of Surgery, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8558, Japan. FAU - Kobayashi, Naoya AU - Kobayashi N FAU - Rivas-Carrillo, Jorge David AU - Rivas-Carrillo JD FAU - Navarro-Alvarez, Nalu AU - Navarro-Alvarez N FAU - Zhao, Debiao AU - Zhao D FAU - Okitsu, Teru AU - Okitsu T FAU - Noguchi, Hirofumi AU - Noguchi H FAU - Basma, Hesham AU - Basma H FAU - Tabata, Yashuhiko AU - Tabata Y FAU - Chen, Yong AU - Chen Y FAU - Tanaka, Kimiaki AU - Tanaka K FAU - Narushima, Michiki AU - Narushima M FAU - Miki, Atsushi AU - Miki A FAU - Ueda, Tadayoshi AU - Ueda T FAU - Jun, Hee-Sook AU - Jun HS FAU - Yoon, Ji-Won AU - Yoon JW FAU - Lebkowski, Jane AU - Lebkowski J FAU - Tanaka, Noriaki AU - Tanaka N FAU - Fox, Ira J AU - Fox IJ LA - eng GR - DK48794/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20061105 PL - United States TA - Nat Biotechnol JT - Nature biotechnology JID - 9604648 RN - 0 (activin A) RN - 103107-01-3 (Fibroblast Growth Factor 2) RN - 104625-48-1 (Activins) RN - 67256-21-7 (Hepatocyte Growth Factor) SB - IM EIN - Nat Biotechnol. 2007 Feb;25(2):254. Zhao, Debaio [corrected to Zhao, Debiao] CIN - Hepatology. 2007 Mar;45(3):829-30. PMID: 17326214 MH - Activins/physiology MH - Animals MH - Cell Culture Techniques/methods MH - Cell Differentiation/*physiology MH - Cell Transplantation/methods/*physiology MH - Embryonic Stem Cells/*physiology/*transplantation MH - Fibroblast Growth Factor 2/physiology MH - Hepatocyte Growth Factor/physiology MH - Hepatocytes/cytology/*physiology MH - Humans MH - Liver Failure, Acute/*therapy MH - *Liver, Artificial MH - Mice MH - Models, Animal EDAT- 2006/11/07 09:00 MHDA- 2006/12/29 09:00 CRDT- 2006/11/07 09:00 PHST- 2006/08/18 00:00 [received] PHST- 2006/10/06 00:00 [accepted] PHST- 2006/11/07 09:00 [pubmed] PHST- 2006/12/29 09:00 [medline] PHST- 2006/11/07 09:00 [entrez] AID - nbt1257 [pii] AID - 10.1038/nbt1257 [doi] PST - ppublish SO - Nat Biotechnol. 2006 Nov;24(11):1412-9. doi: 10.1038/nbt1257. Epub 2006 Nov 5.