Extracellular Vesicles: A Therapeutic Option for Liver Fibrosis

Abstract

Extracellular vesicles (EVs) are a heterogeneous population of small membrane vesicles released by all types of cells in both physiological and pathological conditions. EVs shuttle different types of molecules and are able to modify the behavior of target cells by various mechanisms of action. In this review, we have summarized the papers present in the literature, to our acknowledge, that reported the EV effects on liver diseases. EVs purified from serum, stem cells, and hepatocytes were investigated in different experimental in vivo models of liver injury and in particular of liver fibrosis. Despite the different EV origin and the different types of injury (toxic, ischemic, diet induced, and so on), EVs showed an anti-fibrotic effect. In particular, EVs had the capacities to inhibit activation of hepatic stellate cells, one of the major players of liver fibrosis development; to reduce inflammation and apoptosis; to counteract the oxidative stress; and to increase hepatocyte proliferation, contributing to reducing fibrosis and ameliorating liver function and morphology.

Therapeutic Application of Exosomes in Inflammatory Diseases

“…Liver fibrosis and cirrhosis are lethal diseases that result from chronic liver inflammation [ 109 ], and EVs have been considered as therapeutic agents for such diseases [ 110 , 111 ]. EVs from human amnion-derived MSCs (AM-MSCs) significantly reduced expression of inflammatory cytokines (TNF-α, IL-1β, IL-6, MCP-1, and TGF-β) and M1 macrophage marker proteins (CD68 and CD11c) in the liver tissue of rats in which nonalcoholic steatohepatitis (NASH) had been induced by a high-fat diet (HFD).…”

Molecular Pathways Modulated by Mesenchymal Stromal Cells and Their Extracellular Vesicles in Experimental Models of Liver Fibrosis

“…Extracellular vesicles are small membrane particles delimited by a lipid bilayer membrane that are secreted by virtually all cells into the extracellular microenvironment and can be isolated from all biological fluids. EVs display great heterogeneity in size and molecular cargo, and since specific markers to distinguish one vesicle subpopulation from another are still lacking, EVs are currently classified based on their size and biogenesis in exosomes, ectosomes, and apoptotic bodies (Meldolesi, 2018;Bruno et al, 2020a).…”

Defined MSC exosome with high yield and purity to improve regenerative activity

“… 18 It can be used as an alternative to cell-based therapy that retains the characteristics of the original cells. In particular, MSC-derived exosomes can be applied to various regenerative medicine, including angiogenesis and wound repair, 19 , 20 alleviating liver fibrosis, 21 cardiac repair, 22 neurodegeneration treatment, 23 and osteochondral regeneration. 24 However, there are still barriers to the widespread development of MSC exosome-based therapies for human patients.…”