Figure 15

Origin of MF-like cells and their activation in the scenario of a CLD. Myofibroblast-like cells (MFs) may originate, under CLD conditions, from either quiescent HSCs, portal fibroblasts or bone marrow-derived MSCs able to engraft the chronically injured liver. Whatever the origin, MFs are believed to be characterised by the following properties and phenotypic responses: (a) high proliferative attitude; (b) increased ability to synthesise ECM components, particularly collagen type I and III; (c) altered ability to express matrix metallo-proteinases (MMPs) and related tissue inhibitors (TIMPs), resulting in an altered ability to remodel ECM in excess; (d) increased ability to migrate in response to different stimuli, including truly chemotactic ones; (e) increased synthesis of growth factors and pro-inflammatory cytokines and chemokines [76], including pro-angiogenic cytokines [81, 83, 92, 93], that may act as paracrine as well as autocrine mediators; (f) contractility in response to vasoactive compounds like NO, endothelins and others; (g) the potential to undergo apoptosis in case of removal of the aetiological agent (that is, successful therapy, alcohol withdrawal, and so on) or causative conditions [80, 81, 91], although fibrosis regression has been mainly observed in experimental models. Here it should be mentioned that although there is no doubt that fibrosis is, at least in principle, a potentially reversible process, a complete reversion of cirrhosis (particularly for human cirrhotic livers) has never been convincingly documented [84] and human HSC/MFs have been shown to possess a peculiar survival attitude both in vitro as well as in vivo that may indeed favour progression over reversion [94].