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

Because of a critical shortage in suitable organs, many patients with termi nal liver disease die each year before liver transplantation can be perform ed. Transplantation of isolated hepatocytes has been proposed for the tempo rary metabolic support of patients awaiting liver transplantation or sponta neous reversion of their liver disease. A major limitation of this form of therapy is the present inability to isolate an adequate number of transplan table hepatocytes. A highly differentiated cell line, NKNT-3, was generated by retroviral transfer in normal primary adult human hepatocytes of an imm ortalizing gene that can be subsequently and completely excised by Cre/Lox site-specific recombination. When transplanted into the spleen of rats unde r transient immunosuppression, reversibly immortalized NKNT-3 cells provide d life-saving metabolic support during acute liver failure induced by 90% h epatectomy.