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

Abstract

Aims: It 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 immunophenotypical features similar to those of the oval cells of rodents or the small epithelial cells (SEC) described recently in hepatoblastoma, i.e. putative hepatic progenitor cells, are found in the liver of patients with extrahepatic biliary atresia.

Methods and results: Liver biopsies from 10 infants with extrahepatic biliary atresia were investigated by transmission electron microscopy. Single and double immunolabelling for cytokeratin 7, a marker of biliary differentiation, and albumin, a marker of hepatocytic differentiation, was investigated by immunoelectron microscopy. Electron microscopy revealed SEC that were ultrastructurally similar to the oval cells and coexpressed albumin and cytokeratin 7. The SEC exhibited a spectrum of differentiation that, in addition to relatively undifferentiated cells, included cells that exhibited morphological and immunophenotypical signs of differentiation towards biliary epithelial cells and hepatocytes.

Conclusions: The findings demonstrate that SEC with morphological and immunophenotypical features of the oval cells of rodents and the SEC described in hepatoblastoma are found in the liver of patients with extrahepatic biliary atresia. The data further support the hypothesis that the SEC represent possible candidates for hepatic progenitor cells.