A method of propagating mammalian endodermally derived progenitors such as hepatic progenitors, their progeny, or mixtures thereof is developed which includes culturing mammalian progenitors, their progeny, or mixtures thereof on a layer of embryonic mammalian feeder cells in a culture medium. The culture medium can be supplemented with one or more hormones and other
growth agents. These hormones and other
growth agents can include
insulin,
dexamethasone,
transferrin,
nicotinamide,
serum albumin, beta-mercaptoethanol, free
fatty acid,
glutamine, CUSO4, and H2SeO3. The culture medium can also include
antibiotics. Importantly, the culture medium does not include serum. The invention includes means of inducing the differentiation of the progenitors to their adult fates such as the differentiation of hepatic
progenitor cells to hepatocytes or biliary cells by adding, or excluding
epidermal growth factor, respectively. The method of producing mammalian progenitors is useful in that the progenitors can be used subsequently in one or more of the following processes: identification of growth and differentiation factors, toxicological studies,
drug development,
antimicrobial studies, or the preparation of an
extracorporeal organ such as a bioartificial liver.