Basic Research
Copyright ©2007 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Mar 14, 2007; 13(10): 1554-1560
Published online Mar 14, 2007. doi: 10.3748/wjg.v13.i10.1554
Epithelial cells with hepatobiliary phenotype: Is it another stem cell candidate for healthy adult human liver?
Dung Ngoc Khuu, Mustapha Najimi, Etienne M Sokal
Dung Ngoc Khuu, Mustapha Najimi, Etienne M Sokal, Université Catholique de Louvain, Laboratory of Pediatric Hepatology & Cell therapy, Brussels, Belgium
Author contributions: All authors contributed equally to the work.
Supported by DGTRE, Région Wallonne (Grant Waleo HEPATERA) and by the Fondation saint-Luc. The first author is a recipient of fellowship from FNRS and the Université Catholique de Louvain
Correspondence to: Etienne M Sokal, Université Catholique de Louvain, Cliniques St Luc, 10 av. Hippocrate, B-1200 Brussels, Belgium. sokal@pedi.ucl.ac.be
Telephone: +32-2-7641387 Fax: +32-2-7648909
Received: November 14, 2006
Revised: December 20, 2006
Accepted: February 25, 2007
Published online: March 14, 2007
Abstract

AIM: 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 sub-cultured 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 (α-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.

CONCLUSION: 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.

Keywords: Epithelial-like cells, Liver stem cell, Hepatocyte, Differentiation, Cell therapy