Development of intrahepatic bile ducts in humans. Possible role of laminin

Laminin, a major extracellular matrix-attachment glycoprotein, may play an important role in the differentiation and migration of epithelial cells during normal development. Therefore, the morphogenesis of bile ducts in human liver of fetuses at sequential gestational ages, neonates, children, and adults was examined by single and double immunohistochemical staining for laminin and for cytokeratins. The latter served as a marker for developing and mature bile duct epithelial cells. A close association was observed between laminin deposition and the differentiating ductal plate cells at the epithelial-mesenchymal interface of portal tracts and during the subsequent migration of ductular structures into the center of portal tracts. Simultaneously, laminin disappeared from the margins of portal tracts, but scattered ductal plate-like structures with laminin remained demonstrable in neonates, children, and even adults. These observations were substantiated by semiquantitative evaluation of laminin at the periphery of portal tracts. Thus, clear evidence is provided that laminin accompanies bile duct epithelial cells during all successive stages of differentiation and migration during the development of the human hepatobiliary system. The persisting ductal plate cells may represent a common stem cell for proliferation of bile ductules and hepatocytes.