Hepatic progenitor cells in human fetal liver express the oval cell marker Thy-1

Abstract

Hepatic progenitor cells play a major role in regenerating diseased liver. In rodents, progenitors forming hepatocytes or cholangiocytes are identified by the stem cell marker Thy-1. The aim of this study was to ascertain whether progenitor cells expressing Thy-1 could be identified in human fetal liver. Midtrimester human fetal liver was immunostained for Thy-1, cytokeratins 18 and 19, vimentin, CD34, CD45, and fibrinogen. Thy-1⁺and Thy-1⁺CD34⁺populations were purified using fluorescence-activated cell sorting (FACS). Immunofluorescence and mRNA expression were used to examine the bipotential nature of purified stem cells. We found that Thy-1⁺cells were concentrated in portal tracts but were also scattered in parenchyma. In FACS-prepared cells, 0.18–3.08% (median 0.65%, n = 14) of cells were Thy-1⁺. Immunophenotyping revealed that some Thy-1⁺cells coexpressed cytokeratins 18 and 19, others, fibrinogen and cytokeratin 19. RT-PCR demonstrated that Thy-1⁺cells expressed mRNA for Thy-1, cytokeratin 18, and cytokeratin 19, and Thy-1⁺CD34⁺cells expressed mRNA for α-fetoprotein, transferrin, and hepatocyte nuclear factor-4α. Thy-1⁺cells were identified in fetal liver. These cells expressed several lineage markers, including coexpression of biliary and hepatocellular proteins and mRNA. These data suggest that Thy-1 is a marker of liver stem cells in human fetal liver.