Abstract The definition of hepatic myofibroblasts is currently attributed to a rather heterogenous population of cells that sustain liver fibrogenesis and then fibrotic progression of chronic liver diseases of different aetiology to the common advanced-stage of cirrhosis. These highly proliferative and contractile myofibroblasts actively participate to the progression of the chronic disease by means of their multiple phenotypic responses, including excess deposition of extracellular matrix components and its altered remodelling as well as the synthesis and the release in a paracrine/autocrine way of a number of critical growth factor which sustain and perpetuate fibrogenesis, chronic inflammatory response and neoangiogenesis. According to current literature hepatic myofibroblasts, which are mostly α-smooth muscle actin (α-SMA) - positive cells, mainly originate hepatic stellate cells or from fibroblasts of portal areas through a process of activation and trans-differentiation. Hepatic myofibroblasts have been reported to originate also from bone marrow – derived stem cells, including mesenchymal stem cells or circulating fibrocytes, able to engraft chronically injured liver. It is currently debated whether myofibroblasts may also originate from hepatocytes and cholangiocytes through a process of epithelial to mesenchymal transition. Hepatic myofibroblasts have been reported to play additional crucial roles, including modulation of immune responses in the chronically injured liver and the cross talk with hepatic progenitor (stem) cells as well as with malignant cells of either primary hepatocellular carcinomas or of metastatic cancers.
Hepatic myofibroblasts: origin and role in liver fibrogenesis
NOVO, ERICA;BUSLETTA, CHIARA;PATERNOSTRO, CLAUDIA;POVERO, DAVIDE;CANNITO, STEFANIA;PAROLA, Maurizio
2011-01-01
Abstract
Abstract The definition of hepatic myofibroblasts is currently attributed to a rather heterogenous population of cells that sustain liver fibrogenesis and then fibrotic progression of chronic liver diseases of different aetiology to the common advanced-stage of cirrhosis. These highly proliferative and contractile myofibroblasts actively participate to the progression of the chronic disease by means of their multiple phenotypic responses, including excess deposition of extracellular matrix components and its altered remodelling as well as the synthesis and the release in a paracrine/autocrine way of a number of critical growth factor which sustain and perpetuate fibrogenesis, chronic inflammatory response and neoangiogenesis. According to current literature hepatic myofibroblasts, which are mostly α-smooth muscle actin (α-SMA) - positive cells, mainly originate hepatic stellate cells or from fibroblasts of portal areas through a process of activation and trans-differentiation. Hepatic myofibroblasts have been reported to originate also from bone marrow – derived stem cells, including mesenchymal stem cells or circulating fibrocytes, able to engraft chronically injured liver. It is currently debated whether myofibroblasts may also originate from hepatocytes and cholangiocytes through a process of epithelial to mesenchymal transition. Hepatic myofibroblasts have been reported to play additional crucial roles, including modulation of immune responses in the chronically injured liver and the cross talk with hepatic progenitor (stem) cells as well as with malignant cells of either primary hepatocellular carcinomas or of metastatic cancers.
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