Characterisation of a stereotypical cellular and extracellular adult liver progenitor cell niche in rodents and diseased human liver
- 28 April 2010
- Vol. 59 (5), 645-654
- https://doi.org/10.1136/gut.2009.182345
Abstract
Background Stem/progenitor cell niches in tissues regulate stem/progenitor cell differentiation and proliferation through local signalling. Objective To examine the composition and formation of stem progenitor cell niches. Methods 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. Results 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, γGT) while inhibiting hepatocyte differentiation and gene expression (CEPB/α). Conclusions 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.Keywords
This publication has 32 references indexed in Scilit:
- The isolation and in vitro expansion of hepatic Sca-1 progenitor cellsBiochemical and Biophysical Research Communications, 2009
- Activation of stem cells in hepatic diseasesCell and tissue research, 2007
- The vascular niche and its basement membraneTrends in Cell Biology, 2007
- Side population purified from hepatocellular carcinoma cells harbors cancer stem cell-like propertiesHepatology, 2006
- Intestinal stem cellsJournal of Cellular and Molecular Medicine, 2005
- Nomenclature of the finer branches of the biliary tree: Canals, ductules, and ductular reactions in human liversHepatology, 2004
- Socializing with the NeighborsCell, 2004
- A conserved RNA-binding protein controls germline stem cells in Caenorhabditis elegansNature, 2002
- Wholesale hepatocytic differentiation in the rat from ductular oval cells, the progeny of biliary stem cellsJournal of Hepatology, 1997
- Transforming growth factor β1-regulated gene expression of Ito cellsHepatology, 1996