Epithelial cells with hepatobiliary phenotype: is it another stem cell candidate for healthy adult human liver?
OBJECTIVE
To investigate the presence and role of liver epithelial cells in the healthy human adult liver.


METHODS
Fifteen days after human hepatocyte primary culture, epithelial like cells emerged and started proliferating. Cell colonies were isolated and subcultured for more than 160 d under specific culture conditions. Cells were analyzed for each passage using immunofluorescence, flow cytometry and reverse transcription-polymerase chain reaction (RT-PCR).


RESULTS
Flow cytometry analysis demonstrated that liver epithelial cells expressed common markers for hepatic and stem cells such as CD90, CD44 and CD29 but were negative for CD34 and CD117. Using immunofluorescence we demonstrated that liver epithelial cells expressed not only immature (alpha-fetoprotein) but also differentiated hepatocyte (albumin and CK-18) and biliary markers (CK-7 and 19), whereas they were negative for OV-6. RT-PCR analysis confirmed immunofluorescence data and revealed that liver epithelial cells did not express mature hepatocyte markers such as CYP2B6, CYP3A4 and tyrosine amino-transferase. Purified liver epithelial cells were transplanted into SCID mice. One month after transplantation, albumin positive cell foci were detected in the recipient mouse parenchyma.


CONCLUSIONS
According to their immature and bipotential phenotype, liver epithelial cells might represent a pool of precursors in the healthy human adult liver other than oval cells.
Khuu
Dung-Ngoc
DN
Université Catholique de Louvain, Laboratory of Pediatric Hepatology and Cell Therapy, Brussels, Belgium.
Najimi
Mustapha
M
Sokal
Etienne M
EM
D000293:Adolescent; D000328:Adult; D000818:Animals; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D004847:Epithelial Cells / Q000378:metabolism / Q000637:transplantation*; D005260:Female; D006085:Graft Survival; D006801:Humans; D007097:Imines / Q000378:metabolism; D008099:Liver / Q000166:cytology* / Q000601:surgery; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D010641:Phenotype; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology; D013843:Thiazines / Q000378:metabolism; D000509:alpha-Fetoproteins / Q000378:metabolism
D007097:Imines; D013843:Thiazines; D000509:alpha-Fetoproteins; C091704:CK 17