Immortalization of Differentiated Hepatocytes

The potential uses for continuously proliferating hepatocyte-derived cells have mutiplied in the last thirty years but with this the demand for ever more differentiated functions has grown louder. Amongst the most vociferous lobbies are those of xenobiotic toxicology and recombinant protein technology, two fields where human liver-specific metabolism and polypeptide processing would be advantageous. The development of a bioartificial liver using hepatocyte cell lines instead of primary cells is another application which especially interests us. While current ex vivo liver-support devices containing porcine hepatocytes have been shown to maintain some degree of the complexity of liver functions [1], the low proliferative capacity and rapid loss of specific enzyme activities in primary culture limits their use to the very short-term [2]. Moreover, in the longer term the use of non-human hepatocytes may not confer the required specificity of metabolism.