A reversibly immortalized human hepatocyte cell line as a source of hepatocyte-based biological support

The application of hepatocyte transplantation (HTX) is increasingly envisio ned for temporary metabolic support during acute liver failure and provisio n of specific liver functions in inherited liver-based metabolic diseases. Compared with whole liver transplantation, HTX is a technically simple proc edure and hepatocytes can be cryopreserved for future use. A major limitati on of this form of therapy in humans is the worldwide shortage of human liv ers for isolating an adequate number of transplantable human hepatocyes whe n needed. Fur ther more, the numbers of donor livers available for hepatocy te isolation is limited by competition for their use in whole organ transpl antation. Considering the cost of hepatocyte isolation and the need for imm ediate preparation of consistent and functional cells, it is unlikely that human hepatocytes can be obtained on such a scale to treat a large number o f patients with falling liver functions. The utilization of xenogenic hepat ocytes will result in additional concerns regarding transmission of infecti ous pathogens and immunological and physiological incompatibilities between animals and humans. An attractive alter native to primary human hepatocyte s is the use of tightly regulated human hepatocyte cell lines. Such cell li nes can provide the advantages of unlimited availability, sterility and uni formity. We describe here methods for creating transplantable human hepatoc yte cell lines using currently available cell cultures and gene transfer te chnology.