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Science 18 February 2000:
Vol. 287. no. 5456, pp. 1258 - 1262
DOI: 10.1126/science.287.5456.1258
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Reports

Prevention of Acute Liver Failure in Rats with Reversibly Immortalized Human Hepatocytes

Naoya Kobayashi, 1* Toshiyoshi Fujiwara, 1 Karen A. Westerman, 2 Yusuke Inoue, 3 Masakiyo Sakaguchi, 3 Hirofumi Noguchi, 1 Masahiro Miyazaki, 3 Jin Cai, 4 Noriaki Tanaka, 1 Ira J. Fox, 4* Philippe Leboulch 25*

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.

1 First Department of Surgery and
3 Department of Cell Biology, Okayama University Medical School, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
2 Massachusetts Institute of Technology, Division of Health Sciences and Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA, and Genetix Pharmaceuticals, 840 Memorial Drive, Cambridge, MA 02139, USA.
4 Department of Surgery, University of Nebraska Medical Center, Omaha, NE 68198, USA.
5 Harvard Medical School and Division of Hematology, Department of Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA.
*   To whom correspondence should be addressed. E-mail: ntanaka{at}med.okayama-u.ac.jp (N.K.); ifox{at}surgery.unmc.edu (I.J.F.); paulvw{at}mit.edu (P.L.).

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