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A Novel Cell-Surface Marker Found on Human Embryonic Hepatoblasts and a Subpopulation of Hepatic Biliary Epithelial Cells

^a Monash Institute of Reproduction and Development, Monash University, Victoria, Australia;
^b School of Biosciences, University of Birmingham, and Liver Research Laboratories, Queen Elizabeth University Hospital, Birmingham, United Kingdom

Key Words. Monoclonal antibody GCTM-5 • Embryonic stem cell • Liver stem cell • Differentiation • Endoderm

Correspondence: Martin F. Pera, Ph.D., Monash Institute of Reproduction and Development, Monash University, Clayton 3168, Victoria, Australia. Telephone: 61-3-9594-7318; Fax: 61-3-9594-7311; e-mail: martin.pera{at}med.monash.edu.au

The nature of the cells that contribute to the repopulation of the liver after hepatic necrosis or cirrhosis remains uncertain, in part because we lack specific markers to facilitate identification and prospective isolation of progenitor cells. The monoclonal antibody GCTM-5 reacts with a minority subpopulation of cells in spontaneously differentiating cultures of pluripotent human embryonal carcinoma or embryonic stem cells. The epitope recognized by GCTM-5 is found on a 50-kDa protein present on the surface of these cells. In tissue sections of first-trimester human embryos, GCTM-5 specifically stained hepatoblasts and no other cell type examined. In normal pediatric or adult liver, GCTM-5 reacted with a minority population of luminal bile duct cells. In diseased livers, the numbers of GCTM-5–positive cells were increased compared with normal liver; antibody staining was restricted to a subpopulation of ductular reactive cells, and among this subpopulation we observed GCTM-5–positive cells that did not express cytokeratin 19 or N-CAM, classical makers of ductular reactive cells. Live GCTM-5–positive cells could be isolated from diseased livers by immunomagnetic sorting. These results suggest that GCTM-5 will be a useful reagent for defining cell lineage relationships between putative progenitor populations in embryonic liver and in the biliary epithelium during tissue repair.

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