The finest branches of the biliary tree might induce biliary vascularization necessary for biliary regeneration

Heuvel, Marius C. van den; Gouw, Annette S.H.; Boot, Marcel; Slooff, Maarten J. H.; Poppema, Sibrand; Jong, Koert P. de

doi:10.1016/j.jhep.2005.08.011

Cited by 14 publications

(8 citation statements)

References 35 publications

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“…In patients with episodes of acute rejection (AR) without progression to CR both the microvascular compartment and the biliary tree remained intact. These findings underline the importance of the microvascular compartment of the FBBT during bile duct regeneration (15).…”

Section: Introductionsupporting

confidence: 59%

“…To identify bile ducts, BDL and EXBC and their escorting microvasculature 4‐μm paraffin sections were double immunostained using the mAbs cytokeratin 7 (anticytokeratin 7, DAKO, Glostrup, Denmark, 1/100) and CD34 (anti‐CD34, Qbend clone, Immunotech, Marseille, France, ready to use) as described previously (15). The proliferative activity was studied with the mAb Ki67 (MIB, DAKO, dilution 1/400).…”

Section: Methodsmentioning

confidence: 99%

“…This suggests that the integrity of the FBBT must be maintained to enable an adequate regenerative response of the biliary tree and to prevent the development of ductopenia. Loss of the FBBT was found to be associated with insufficient recovery of microvasculature accompanying the FBBT (15). In patients with episodes of acute rejection (AR) without progression to CR both the microvascular compartment and the biliary tree remained intact.…”

Section: Introductionmentioning

confidence: 99%

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Preservation of Bile Ductules Mitigates Bile Duct Loss

Heuvel¹,

Jong

Boot³

et al. 2006

American Journal of Transplantation

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The finer branches of the biliary tree (FBBT) contain a regenerative compartment. We hypothesized that preservation of the FBBT together with its microvasculature will lead to recovery of biliary damage and prolonged preservation of bile ductules during the development of chronic liver allograft rejection.The interlobular bile ducts, portal bile ductules and extraportal biliary cells with and without microvessels were studied in sequential biopsies in five patients who fulfilled the Banff criteria of early chronic rejection (CR) (imminence group). Biopsies of CR patients (n = 12) served as controls. Biopsies were double immunostained with CD34 (microvessels) and cytokeratin 7 (biliary structures). Proliferation and proangiogenic activity were assessed with Ki67 and VEGF-A immunostaining.Severe damage of bile ducts in the imminence group did not progress to significant bile duct loss. This was associated with a high proliferative activity in all biliary structures and preservation of the microvascular compartment. VEGF-A expression was increased in all but the reperfusion biopsies.In conclusion, both regenerative activity of the FBBT and an intact microvascular compartment are associated with less damage of the biliary tree and could therefore be prerequisites for biliary regeneration.

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Section: Introductionsupporting

confidence: 59%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Preservation of Bile Ductules Mitigates Bile Duct Loss

Heuvel¹,

Jong

Boot³

et al. 2006

American Journal of Transplantation

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“…These can be considered as different transformation stages between sinusoids and small portal venules, compatible with the so-called "portalized sinusoids" according to Ekataksin and Wake [10,18]. Immunohistochemical studies of the vasculature in DR in human liver have further shown that ductules and vessels react in unison, and that-like in the embryonic period [19]-the ductules precede and induce [20] and also maintain [21] their . Cirrhotic stage of liver in biopsy from patient with non-alcoholic steato-hepatitis (NASH).…”

Section: Ductal Plate Configuration In Ductular Reactionmentioning

confidence: 81%

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

Desmet

2011

Virchows Arch

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This article discusses the processes of bile duct growth and new lobule formation in the liver during childhood in the light of the ductal plate (DP) hypothesis. Unlike in other organs in which tubular elongation and branching ends with the creation of the organ-specific terminal differentiation products, in the liver a steadily enlarging parenchymal mass needs to establish continuity of its canalicular network with the existing bile duct system. The hypothesis suggests that this occurs by DP formation, like in the embryonic liver, and further assumes that pathological ductular reactions (DRs) induced by cholestasis or hypoxia are amplified equivalents of similar mechanisms operating at low level during liver growth. The concept is confronted with data on porcine liver growth, since swine and non-swine liver growth is thought to be comparable. Relative bile acid load may be the driving force for establishment of new canaliculo-ductular connections, supported in zones of relative hypoxia by hypoxia-inducible factor 1 alpha secreted by hepatocytes. The latter mechanism is at the base for induction of appropriate vascular changes in selected sinusoids, resulting in the development of portal inlet venules and additional draining central veins. The process gives rise to the formation of new single lobules by formation of new portal tracts or to the transformation of single lobules in compound lobules by development of new vascular septa. The concept of postnatal DP formation is important in the elucidation of several unexplained findings in adult liver diseases.

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“…Cell loss will be healed thereafter with compensatory biliary proliferation, and in the way that the tissue integrity should be preserved: Neovascularization and tissue remodeling/matrix production seem to be prerequisite. In fact, bile duct proliferation followed by hepatic artery neovascularization was shown by 3‐dimensional imaging studies in rats, 2 and this sequence was recently confirmed by immunohistochemical studies in human transplants, with a special emphasis on vascular endothelial growth factor (VEGF)‐A expression on IBEC 3 . Accordingly, IBEC are increasingly gaining attention as an active contributor to liver regeneration, though their excess activation may result in portal fibrosis.…”

Section: Introductionmentioning

confidence: 85%