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Insertion of a Suicide Gene Into an Immortalized Human Hepatocyte Cell Line

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For developing a bioartificial liver (BAL) device, an attractive alternative to the primary human hepatocytes would be the use of highly differentiated immortalized human hepatocytes with a safeguard. To test the feasibility, the primary human hepatocytes were immortalized by a plasmid SV3neo encoding simian virus 40 large T antigen (SV40Tag) gene. A highly differentiated hepatocyte line OUMS-29 was established. A suicide gene of herpes simplex virus-thymidine kinase (HSV-TK) was retrovirally introduced into OUMS-29 cells as a safeguard for clinical application. One of the resulting HSV-TK-positive cell lines, OUMS-29/tk, grew in chemically defined serum-free medium with the gene expression of differentiated liver functions. OUMS-29/tk cells were 100 times more sensitive to ganciclovir compared with unmodified OUMS-29 cells in in vitro experiments. We have established a tightly regulated immortalized human hepatocyte cell line. Essentially unlimited availability of OUMS-29/tk cells may be clinically useful for BAL therapy.

Keywords: Key words: Immoralized human hepatocytes; Suicide

Document Type: Research Article


Affiliations: 1: *First Department of Surgery, Okayama University Medical School, 2-5-1 Shikata-cho, Okayama 700-8558, Japan 2: †Department of Cell Biology, Okayama University Medical School, 2-5-1 Shikata-cho, Okayama 700-8558, Japan

Publication date: 2001-04-01

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