The present invention provides clonal pluripotent hepatic stem cells using
flow cytometry and in vitro single-cell-based assays. These cells possess
multilineage differentiation potential and self-renewing capability.
These cells may be clonally propagated in culture, to continuously
produce hepatocytes and cholangiocytes as descendants while maintaining
primitive stem cells. When expanded cells are transplanted into recipient
animals, they morphologically and functionally differentiated into
hepatocytes and cholangiocytes, with reconstitution of hepatocyte and
bile duct structures. Furthermore, these cells differentiated into
pancreatic ductal and acinar cells or intestinal epithelial cells when
transplanted into pancreas or duodenal wall. Thus, the self-renewing
multipotent stem cells persist in the developing mouse liver and can be
induced to become cells of other organs of endodermal origin under
appropriate microenvironment, providing new insight into therapies for
diseases of the digestive system.