Ductal plates in hepatic ductular reactions. Hypothesis and implications. III. Implications for liver pathology

Desmet, Valeer

doi:10.1007/s00428-011-1050-9

Cited by 39 publications

(40 citation statements)

References 72 publications

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“…These ensure the adequate vascularization and biliary drainage of new choleohepatons during enlargement of existing lobules and are the base of ongoing lobulogenesis during liver growth. The proposal that DRs in DP form play a role during normal liver growth in childhood is indirectly supported by several observations in pathological conditions of the liver, including von Meyenburg complexes, Alagille syndrome, and biliary atresia, discussed in a separate paper [45].…”

Section: Resultsmentioning

confidence: 97%

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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Section: Resultsmentioning

confidence: 97%

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

Desmet

2011

Virchows Arch

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“…Although parenchymal cells are almost completely lost in the process of MHN, the liver still demonstrates an enormous regenerative capability to restore liver parenchyma and function, which is thought to be dependent on liver progenitor cells residing in the Canals of Hering and the ductules (Gouw et al, 2011; Desmet, 2011a,b; Itoh and Miyajima, 2014). The final clinical outcome is dependent on whether the massive parenchymal loss can be rapidly compensated by LPC-mediated regeneration.…”

Section: Liver Progenitor Cells Mediate Liver Regeneration In Mhnmentioning

confidence: 99%

“…DR may arise from different cell sources in different settings, including (1) proliferation of pre-existing cholangiocytes; (2) liver progenitor cells (local and/or circulating cells probably bone marrow-derived); (3) rarely, biliary metaplasia of hepatocytes; (4) hepatocytes (Desmet, 2011b). In MHN, LPCs are the predominant cell source of DR because most parenchymal cells die in this setting.…”

Section: Liver Progenitor Cells Mediate Liver Regeneration In Mhnmentioning

confidence: 99%

“…Livers of the patients recovered from ALF or ACLF demonstrate a remarkable regenerative capacity to rapidly restore lost parenchymal cells and corresponding functions. This pattern of liver regeneration is thought to be mediated by liver progenitor cells (LPC) (Desmet, 2011a,b) and entitled the “second pathway of liver regeneration” to be distinguished from the “first pathway of liver regeneration,” in which repopulation of the liver is dependent on the remaining mature hepatocytes (Clouston et al, 2009). Necrosis and LPC-mediated regeneration comprise two sides of one coin, the balance of which determines the destiny of patients suffering from MHN.…”

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confidence: 99%

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Two sides of one coin: massive hepatic necrosis and progenitor cell-mediated regeneration in acute liver failure

et al. 2015

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Massive hepatic necrosis is a key event underlying acute liver failure, a serious clinical syndrome with high mortality. Massive hepatic necrosis in acute liver failure has unique pathophysiological characteristics including extremely rapid parenchymal cell death and removal. On the other hand, massive necrosis rapidly induces the activation of liver progenitor cells, the so-called “second pathway of liver regeneration.” The final clinical outcome of acute liver failure depends on whether liver progenitor cell-mediated regeneration can efficiently restore parenchymal mass and function within a short time. This review summarizes the current knowledge regarding massive hepatic necrosis and liver progenitor cell-mediated regeneration in patients with acute liver failure, the two sides of one coin.

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“…[5][6][7][8][9][10][11][12][13][14] At the histological level, cirrhotic livers display a diversity of parenchymal cell morphology, including small and large hepatocytes, as well as, additional epithelial cell types in ductular or periductular areas. [15][16][17][18][19][20][21] Some of these cells may include adult stem/progenitor cell populations. The canals of Herring in periductular areas have been identified as a source of progenitor cells in adult human liver.…”

Section: Introductionmentioning

confidence: 99%

Triple Staining Including FOXA2 Identifies Stem Cell Lineages Undergoing Hepatic and Biliary Differentiation in Cirrhotic Human Liver

Rogler

Remon

Matarlo

et al. 2016

J Histochem Cytochem.

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SummaryRecent investigations have reported many markers associated with human liver stem/progenitor cells, "oval cells," and identified "niches" in diseased livers where stem cells occur. However, there has remained a need to identify entire lineages of stem cells as they differentiate into bile ducts or hepatocytes. We have used combined immunohistochemical staining for a marker of hepatic commitment and specification (FOXA2 [Forkhead box A2]), hepatocyte maturation (Albumin and HepPar1), and features of bile ducts (CK19 [cytokeratin 19]) to identify lineages of stem cells differentiating toward the hepatocytic or bile ductular compartments of end-stage cirrhotic human liver. We identified large clusters of disorganized, FOXA2 expressing, oval cells in localized liver regions surrounded by fibrotic matrix, designated as "micro-niches." Specific FOXA2-positive cells within the micro-niches organize into primitive duct structures that support both hepatocytic and bile ductular differentiation enabling identification of entire lineages of cells forming the two types of structures. We also detected expression of hsa-miR-122 in primitive ductular reactions expected for hepatocytic differentiation and hsa-miR23b cluster expression that drives liver cell fate decisions in cells undergoing lineage commitment. Our data establish the foundation for a mechanistic hypothesis on how stem cell lineages progress in specialized micro-niches in cirrhotic endstage liver disease. (J Histochem Cytochem 65:33-46, 2017)

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Ductal plates in hepatic ductular reactions. Hypothesis and implications. III. Implications for liver pathology

Cited by 39 publications

References 72 publications

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

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

Two sides of one coin: massive hepatic necrosis and progenitor cell-mediated regeneration in acute liver failure

Triple Staining Including FOXA2 Identifies Stem Cell Lineages Undergoing Hepatic and Biliary Differentiation in Cirrhotic Human Liver

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