Architectural and Immunohistochemical Characterization of Biliary Ductules in Normal Human Liver

Abstract

The canals of Hering or biliary ductules have been described to connect the bile canaliculi with the interlobular bile ducts, and thus forming the distal part of the biliary tree. Studies in the last two decades suggested that the cells constructing these ductules could behave as hepatic progenitor cells. The canals of Hering are confined to the periportal space in the rat, while they have been reported to spread beyond the limiting plate in human liver. The distribution of the distal biliary ductules in normal human hepatic tissue has been investigated in our recent experiments. We could demonstrate the presence of interlobular connective tissue septa in a rudimentary form in healthy livers. The canals of Hering run in these septa in line with the terminal branches of the portal vein and hepatic arteries. This arrangement develops in the postnatal period but regresses after early childhood. The canals of Hering can be identified by the unique epithelial membrane antigen (EMA)-/CD56+/CD133+ immunophenotype. The canals of Hering leave the periportal space and spread into the liver parenchyma along rudimentary interlobular septa outlining the hepatic lobules. Our observations refine the original architectural description of the intraparenchymal portion of the canals of Hering in the human liver. The distinct immunophenotype supports their unique biological function.

Expression of Tight Junction Components in Hepatocyte-Like Cells Differentiated from Human Embryonic Stem Cells

“…Changes in the marker gene, ABC transporter gene and TJ gene expression patterns in our experiments may reflect the in vivo hepatocyte differentiation process. Expression patterns of the hepatocytespecific genes, ABC transporter genes and the TJ genes observed in our study were typical for cells having both hepatocyte and cholangiocyte characteristics [13]. This may be caused by complete polarization of cells, which also observed in hepatocytes during development, leading to adequate targeting of proteins specific to the canalicular membrane [13,14,21] .…”

“…Expression patterns of the hepatocytespecific genes, ABC transporter genes and the TJ genes observed in our study were typical for cells having both hepatocyte and cholangiocyte characteristics [13]. This may be caused by complete polarization of cells, which also observed in hepatocytes during development, leading to adequate targeting of proteins specific to the canalicular membrane [13,14,21] . Our study indicates that the main cell types in the heterogeneous cell cultures obtained by the end of the hepatic differentiation of HUES9 cells were almost matured hepatocytes and cholangiocytes.…”

“…Consequently, the biliary type cytokeratins, CK-7, CK-8, CK-18, and CK-19 are highly expressed in cholangiocarcinomas [12,13]. 4 Hepatic ABC transporters greatly contribute to various functions of liver cells.…”

Ductal plates in hepatic ductular reactions. Hypothesis and implications. II. Ontogenic liver growth in childhood

“…According to the latter authors, the similarity between the vascular septum in Matsumoto's lobular concept of the human liver [11,12] and the pre-fibrous septation stages in pig liver imply that lobulation in suine and nonsuine livers is based on essentially identical designs [18]. The similarity with pig liver was confirmed in a later study, which revealed in healthy human livers during the postnatal period interlobular connective tissue septa in a rudimentary form, which regress after early childhood [27]. The following section emphasizes the similarity in the process of new liver unit formation with that of portal tract development during embryonic and fetal development and compares the proposals of the hypothesis with the previously published observations on new lobule formation in the porcine liver.…”

“…The vascular septum represents the periphery of the liver lobule, and hence, the periphery of its composing choleohepatons. A choleohepaton can be viewed as a coneshaped smaller structure, arranged with its base against the vascular septum and pointing towards the central vein; each choleohepaton has a venule and a ductule running as a couplet together in the vascular septum, adjoined by an arteriolar capillary [18,27]. It is composed of a pyramidal group of a few liver cell plates and their interposed sinusoids (the "hepatic microcirculatory subunit" ; Fig.…”