Small epithelial cells in extrahepatic biliary atresia: electron microscopic and immunoelectron microscopic findings suggest a close relationship to liver progenitor cells

Aims: Tt is still unclear whether hepatic stem cells that give rise to both biliary epithelial cells and hepatocytes exist in the human liver The aim of this study was to investigate whether cells with ultrastructural and imm unophenotypical features similar to those of the oval cells of rodents or t he small epithelial cells (SEC) described recently in hepatoblastoma, i.e. putative hepatic progenitor cells, are found in the liver of patients with extrahepatic bilary atresia. Methods and results: Liver biopsies from 10 infants with extrahepatic bilia ry atresia were investigated by transmission electron microscopy. Single an d double immunolabelling for cytokeratin 7, a marker of biliary differentia tion, and albumin, a marker of hepatocytic differentiation, was investigate d by immunoelectron microscopy. Electron microscopy revealed SEC that were ultrastructurally similar to the oval cells and coexpressed albumin and cyt okeratin 7. The SEC exhibited a spectrum of differentiation that, in additi on to relatively undifferentiated cells, included cells that exhibited morp hological and immunophenotypical signs of differentiation towards biliary e pithelial cells and hepatocytes. Conclusions: The findings demonstrate that SEC with morphological and immun ophenotypical features of the oval cells of rodents and the SEC described i n hepatoblastoma are found in the liver of patients with extrahepatic bilia ry atresia. The data further support the hypothesis that the SEC represent possible candidates for hepatic progenitor cells.