Prevention of acute liver failure in rats with reversibly immortalized human hepatocytes

Naoya Kobayashi, Toshiyoshi Fujiwara, Karen A. Westerman, Yusuke Inoue, Masakiyo Sakaguchi, Hirofumi Noguchi, Masahiro Miyazaki, Jin Cai, Noriaki Tanaka, Ira J. Fox, Philippe Leboulch

Research output: Contribution to journalArticle

290 Citations (Scopus)

Abstract

Because of a critical shortage in suitable organs, many patients with terminal liver disease die each year before liver transplantation can be performed. Transplantation of isolated hepatocytes has been proposed for the temporary metabolic support of patients awaiting liver transplantation or spontaneous reversion of their liver disease. A major limitation of this form of therapy is the present inability to isolate an adequate number of transplantable hepatocytes. A highly differentiated cell line, NKNT-3, was generated by retroviral transfer in normal primary adult human hepatocytes of an immortalizing gene that can be subsequently and completely excised by Cre/Lox site-specific recombination. When transplanted into the spleen of rats under transient immunosuppression, reversibly immortalized NKNT-3 cells provided life-saving metabolic support during acute liver failure induced by 90% hepatectomy.

Original languageEnglish
Pages (from-to)1258-1262
Number of pages5
JournalScience
Volume287
Issue number5456
DOIs
Publication statusPublished - Feb 18 2000
Externally publishedYes

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Acute Liver Failure
Hepatocytes
Liver Transplantation
Liver Diseases
Hepatectomy
Immunosuppression
Genetic Recombination
Spleen
Transplantation
Cell Line
Genes
Therapeutics

ASJC Scopus subject areas

  • General

Cite this

Prevention of acute liver failure in rats with reversibly immortalized human hepatocytes. / Kobayashi, Naoya; Fujiwara, Toshiyoshi; Westerman, Karen A.; Inoue, Yusuke; Sakaguchi, Masakiyo; Noguchi, Hirofumi; Miyazaki, Masahiro; Cai, Jin; Tanaka, Noriaki; Fox, Ira J.; Leboulch, Philippe.

In: Science, Vol. 287, No. 5456, 18.02.2000, p. 1258-1262.

Research output: Contribution to journalArticle

Kobayashi, N, Fujiwara, T, Westerman, KA, Inoue, Y, Sakaguchi, M, Noguchi, H, Miyazaki, M, Cai, J, Tanaka, N, Fox, IJ & Leboulch, P 2000, 'Prevention of acute liver failure in rats with reversibly immortalized human hepatocytes', Science, vol. 287, no. 5456, pp. 1258-1262. https://doi.org/10.1126/science.287.5456.1258
Kobayashi, Naoya ; Fujiwara, Toshiyoshi ; Westerman, Karen A. ; Inoue, Yusuke ; Sakaguchi, Masakiyo ; Noguchi, Hirofumi ; Miyazaki, Masahiro ; Cai, Jin ; Tanaka, Noriaki ; Fox, Ira J. ; Leboulch, Philippe. / Prevention of acute liver failure in rats with reversibly immortalized human hepatocytes. In: Science. 2000 ; Vol. 287, No. 5456. pp. 1258-1262.
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