Human hepatic stem-like cells isolated using c-kit or CD34 can differentiate into biliary epithelium

Background & Aims: Recent reports suggest that after bone marrow transplant ation into rodents and humans, hematopoietic stem cells migrate into the li ver and give rise to oval cells, hepatocytes, and biliary epithelial cells. We investigated this hypothesis further in the human liver using the hemat opoietic markers c-kit and CD34. Methods: Immunofluorescence confocal micro scopy was performed using cytokeratin 19 (CK-19; biliary cell marker) with either c-kit or CD34. Immunomagnetic separation was then used to select c-h it- or CD34-positive cells. After attachment, cells were cultured for up to 7 days, and their growth and phenotypic characteristics were examined. Res ults: In cirrhotic tissue, c-kit- or CD34-positive cells were located in th e portal tracts surrounding bile ducts. Occasionally c-kit- (but not CD34-) positive cells that coexpressed CK-19 were observed integrated into bile d ucts. In vitro, immunoisolated c-kit or CD34 cells gave rise to colonies of at least 2 morphologies expressing CK-19 or CD31 (endothelial cell marker) . CD34- or c-hit-positive cells with similar properties were also isolated from normal liver. Conclusions: These findings indicate that cells present in human liver that express the markers c-kit or CD34 have the capacity to differentiate into biliary epithelial cell lineage and may therefore repres ent human biliary epithelial progenitor cells.