The present invention is directed to methods for readily generating
hepatocyte precursor cell lines that retain hepatocyte-specific functions
after extensive in vitro culturing. The methods comprise isolating and
culturing hepatocyte precursor cell lines under permissive culture
conditions that suppress asymmetric cell kinetics and allow exponential
growth of the precursor cells, followed by transferring the hepatocyte
precursor cell lines to non-permissive culture conditions that allow
expression of asymmetric cell kinetics and induce expression of
hepatocyte-specific characteristics.