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: 10.73). 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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    Liver international: official journal of the International Association for the Study of the Liver 03/2014; · 3.87 Impact Factor
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    Liver international: official journal of the International Association for the Study of the Liver 04/2014; · 3.87 Impact Factor
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    ABSTRACT: The hepatic progenitor cell (HPC) niche is a special microenvironment composed of different cell types, extracellular matrix (ECM) components, growth factors and cytokines released by the niche cells that help to maintain the characteristics of HPCs and the balance between their activation, proliferation and differentiation. Composition of this special microenvironment, created in response to specific liver damage, together with critical interactions between different partners of the HPC niche can determine the fate decision and differentiation pathways of HPCs. A number of recent studies have shed light on factors and signals from the HPC niche that determines the choice of HPCs differentiation towards a specific cell type depending on the nature of the liver injury and resultant microenvironment created by this injury. This paper seeks to provide an in-depth review, through a literature review and the authors' experiences, of the most recent findings on the role of the HPC niche in fate choice option of HPCs toward either hepatocytes or bile duct epithelial cells and its clinical relevance.
    Middle East journal of digestive diseases. 04/2014; 6(2):57-64.

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