Characterisation of a stereotypical cellular and extracellular adult liver progenitor cell niche in rodents and diseased human liver

MRC/University of Edinburgh Centre for Inflammation Research, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh, UK.
Gut (Impact Factor: 13.32). 05/2010; 59(5):645-54. DOI: 10.1136/gut.2009.182345
Source: PubMed

ABSTRACT Stem/progenitor cell niches in tissues regulate stem/progenitor cell differentiation and proliferation through local signalling.
To examine the composition and formation of stem progenitor cell niches.
The composition of the hepatic progenitor cell niche in independent models of liver injury and hepatic progenitor cell activation in rodents and humans was studied. To identify the origin of the progenitor and niche cells, sex-mismatched bone marrow transplants in mice, who had received the choline-ethionine-deficient-diet to induce liver injury and progenitor cell activation, were used. The matrix surrounding the progenitor cells was described by immunohistochemical staining and its functional role controlling progenitor cell behaviour was studied in cell culture experiments using different matrix layers.
The progenitor cell response in liver injury is intimately surrounded by myofibroblasts and macrophages, and to a lesser extent by endothelial cells. Hepatic progenitor cells are not of bone marrow origin; however, bone marrow-derived cells associate intimately with these cells and are macrophages. Laminin always surrounds the progenitor cells. In vitro studies showed that laminin aids maintenance of progenitor and biliary cell phenotype and promotes their gene expression (Dlk1, Aquaporin 1, gammaGT) while inhibiting hepatocyte differentiation and gene expression (CEPB/alpha).
During liver damage in rodents and humans a stereotypical cellular and laminin niche forms around hepatic progenitor cells. Laminin helps maintenance of undifferentiated progenitor cells. The niche links the intrahepatic progenitor cells with bone marrow-derived cells and links tissue damage with progenitor cell-mediated tissue repair.

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Available from: Kay Samuel, Aug 10, 2015
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    • "The liver ECM has the individuality of the basement membrane absence and the ECM is a thin layer consisting mostly of fibronectin, some collagen type I, and minor quantities of types III, IV, V, and VI, which favour a rapid bidireccional exchange of macromolecules between plasma and hepatocytes. In addition, the hepatic stellate cell (HSC) niche is rich in laminin (Lorenzini et al., 2010) The basolateral surface of the hepatocytes are responsible for the transport of proteins and other plasma components into the perisinusoidal space, and the apical surface is responsible for the transport of bile acids and bile salts into the canaliculus that surrounds the hepatocyte. "
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