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

Lorenzini S., Bird T.G., Boulter L., Bellamy C., Samuel K., Aucott R., Clayton E., Andreone P., Bernardi M., Golding M., Alison M.R., Iredale J.P., Forbes S.J.Gut, 2010


In this article, the composition and formation of stem progenitor cell niches were examined. 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 the 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 the 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.