Human hepatic stem-like cells isolated using c-kit or CD34 can differentiate into biliary epithelium.
OBJECTIVE
Recent reports suggest that after bone marrow transplantation into rodents and humans, hematopoietic stem cells migrate into the liver and give rise to oval cells, hepatocytes, and biliary epithelial cells. We investigated this hypothesis further in the human liver using the hematopoietic markers c-kit and CD34.


METHODS
Immunofluorescence confocal microscopy was performed using cytokeratin 19 (CK-19; biliary cell marker) with either c-kit or CD34. Immunomagnetic separation was then used to select c-kit- or CD34-positive cells. After attachment, cells were cultured for up to 7 days, and their growth and phenotypic characteristics were examined.


RESULTS
In cirrhotic tissue, c-kit- or CD34-positive cells were located in the portal tracts surrounding bile ducts. Occasionally c-kit- (but not CD34-) positive cells that coexpressed CK-19 were observed integrated into bile ducts. 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-kit-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 represent human biliary epithelial progenitor cells.
Crosby
H A
HA
School of Biosciences, University of Birmingham, England. H.A.CROSBY.BCM@bham.ac.uk
Kelly
D A
DA
Strain
A J
AJ
D000328:Adult; D018952:Antigens, CD34 / Q000032:analysis*; D000954:Antigens, Surface / Q000032:analysis; D015415:Biomarkers; D014408:Biomarkers, Tumor; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D019070:Cell Lineage / Q000502:physiology; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000737:chemistry / Q000166:cytology*; D005455:Fluorescent Antibody Technique; D006412:Hematopoietic Stem Cells / Q000737:chemistry / Q000166:cytology*; D006801:Humans; D016130:Immunophenotyping; D008099:Liver / Q000166:cytology*; D008103:Liver Cirrhosis / Q000473:pathology; D008875:Middle Aged; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis*; D013194:Staining and Labeling; D000951:Antigens, Neoplasm
D018952:Antigens, CD34; D000954:Antigens, Surface; D015415:Biomarkers; D014408:Biomarkers, Tumor; D019009:Proto-Oncogene Proteins c-kit; C115012:human epithelial antigen-125; D000951:Antigens, Neoplasm