Cholangiocytes (epithelial cells lining the intra- and extrahepatic bile ducts) and hepatocytes are two major components of liver epithelia. Although cholangiocytes are less numerous than hepatocytes, they are involved in both bile secretion and diverse cellular processes such as cell-cycle phenomena, cell signaling, and interactions with other cells, matrix components, foreign organisms, and xenobiotics. Cholangiocytes are also targets in several human diseases including cholangiocarcinoma, primary sclerosing cholangitis, autoimmune cholangitis, and vanishing bile-duct syndrome. The rapid advances in experimental biology technologies are greatly expanding interest in and knowledge of the physiology and pathophysiology of cholangiocytes. This review focuses on the progress of in vivo and in vitro experimental models in elucidating the physiologic functions of cholangiocytes and the pathophysiology of various cholangiopathies. The following aspects are reviewed: isolation of cholangiocytes from the liver and their heterogeneity, various culture systems, establishment of cholangiocyte cell lines, isolation and usage of intrahepatic bile-duct units, three-dimensional modeling of the bile duct, experimental models for inducing cholangiocyte proliferation, and various cholangiopathies such as cholangiocarcinoma, primary sclerosing cholangitis, and autoimmune cholangitis.
Animals ; Bile Duct Diseases/etiology ; Bile Ducts/*cytology/physiology/*physiopathology ; Disease Models, Animal ; Epithelial Cells/metabolism/physiology ; Humans ; Imaging, Three-Dimensional ; Mice ; Models, Animal

OBJECTIVETo study the effect of heme oxygenase-1 (HO-1) on peribiliary vascular plexus (PVP) in rat bile duct ischemia/reperfusion injury.

METHODSTotal 128 male SD rats were randomly divided into saline group (Saline), empty virus group (Adv), induced group (Adv-HO-1) and suppressed group (HO-1 siRNA), and there were 32 rats in each group. Rats were injected using 0.5 ml of saline, empty adenovirus, HO-1 adenovirus and siRNA adenovirus (2×10(9) TU/rat) via the dorsal penile vein 24 hours before surgery. Liver function was analyzed at 1 hour and 1, 7, 14 days after reperfusion. HO-1, hypoxiainducible factor-1α (HIF-1α), stromal cell derived factor-1α (SDF-1α) and vascular endothelial growth factor (VEGF) protein content was analyzed by Western blot. The endothelial progenitor cells (EPCs) ratio in the liver and peripheral blood was detected by flow cytometry. Small vascular around the bile duct was observed by α-smooth muscle actin and von Willebrand factor double immunofluorescence staining.

RESULTSReduced liver injury and higher expression of HIF-1α, SDF-1α and VEGF in the induced group after surgery (q = 5.68-7.52, P < 0.01). EPCs ratio in the liver and peripheral blood was significantly higher in the induced group than saline group (q = 12.14 and 15.26, P < 0.01), and the suppressed group at 7 days after surgery were less than saline group significantly (q = 4.83 and 5.07, P < 0.01). In comparison to the suppressed group, higher density of small vascular around the bile duct was seen in the liver tissue of induced group.

CONCLUSIONSHO-1 can induce the expression of HIF-1α, SDF-1α and VEGF, and mobilize the release of EPCs to the peripheral from the bone marrow. EPCs migrate to the liver and promote damaged PVP repair and regeneration.

Animals ; Bile Ducts ; blood supply ; Chemokine CXCL12 ; metabolism ; Endothelial Cells ; cytology ; Heme Oxygenase (Decyclizing) ; physiology ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; Male ; Neovascularization, Physiologic ; RNA, Small Interfering ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; physiopathology ; Stem Cells ; cytology ; Vascular Endothelial Growth Factor A ; metabolism