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, CuSO.sub.4,
and H.sub.2SeO.sub.3. 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.