| Survival of liver failure pigs by transplantation of reversibly immortalized human hepatocytes with Tamoxifen-mediated self-recombination. | |
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MedLine Citation:
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PMID: 17434229 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND/AIMS: Hepatocyte transplantation and bioartificial liver treatment are attractive alternatives to liver transplantation. The availability of well-characterized human hepatocyte lines facilitates such cell therapies. METHODS: Human hepatocytes were immortalized with a retroviral vector SSR#197 expressing catalytic subunit of human telomerase reverse transcriptase (hTERT) and enhanced green fluorescent protein (EGFP) cDNAs flanked by a pair of loxP recombination targets. Then, Tamoxifen-dependent Cre recombinase was expressed in SSR#197-immortalized hepatocytes. Cre/LoxP recombination was performed in the established cells by simple exposure to 500 nM Tamoxifen for a week. Then, the reverted population of the cells was recovered by EGFP-negative cell sorting and characterized in vitro and in vivo using a pig model of acute liver failure (ALF) induced by d-galactosamine (0.5 g/kg) injection. RESULTS: A human hepatocyte cell line 16T-3 was established. Reverted 16-T3 cells showed the increased expression of hepatic markers in association with enhanced levels of transcriptional factors. Compared to normal human hepatocytes, albumin production and lidocaine-metabolizing activities of reverted 16-T3 cells were 0.32 and 0.50-fold, respectively. Transplantation of reverted 16T-3 cells significantly prolonged the survival of ALF pigs. CONCLUSIONS: Here we demonstrate the usefulness of Cre/LoxP -mediated reversible immortalization of human hepatocytes with Tamoxifen-mediated self-recombination. |
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Authors:
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Toshinori Totsugawa; Chen Yong; Jorge David Rivas-Carrillo; Alejandro Soto-Gutierrez; Nalú Navarro-Alvarez; Hirofumi Noguchi; Teru Okitsu; Karen A Westerman; Michinori Kohara; Michael Reth; Noriaki Tanaka; Philippe Leboulch; Naoya Kobayashi |
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Publication Detail:
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Type: Journal Article Date: 2007-03-15 |
Journal Detail:
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Title: Journal of hepatology Volume: 47 ISSN: 0168-8278 ISO Abbreviation: J. Hepatol. Publication Date: 2007 Jul |
Date Detail:
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Created Date: 2007-06-04 Completed Date: 2007-09-13 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8503886 Medline TA: J Hepatol Country: England |
Other Details:
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Languages: eng Pagination: 74-82 Citation Subset: IM |
Affiliation:
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Department of Surgery, Okayama University Graduate School of Medicine and Dentistry, Okayama 700-8558, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Biological Markers / analysis Cell Line, Transformed / chemistry, cytology, transplantation* Hepatocytes / chemistry, drug effects, transplantation* Humans Integrases / genetics Liver Failure / pathology, surgery* Recombination, Genetic Retroviridae / genetics Sus scrofa Tamoxifen / pharmacology Treatment Outcome |
| Chemical | |
Reg. No./Substance:
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0/Biological Markers; 10540-29-1/Tamoxifen; EC 2.7.7.-/Cre recombinase; EC 2.7.7.-/Integrases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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