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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.
Highlights
Different types of injury may induce acute liver damage, which can elicit tissue inflammation
extracellular vesicles (EVs) derived from human bone marrow (BM)-mesenchymal stromal cell (MSC) have shown similar effects in a rat model of CCl4 -induced liver fibrosis, and the reduced hepatic stellate cells’ (HSCs) activation has been linked to the inhibition of several genes in the Wnt signalin pathway, such as peroxisome proliferator-activated receptor (PPAR)-gamma, beta-catenin, WNT3a, and WNT10b
Despite that the benefits of EVs in different models of liver damage, in particular in fibrosis, have been extensively evaluated, further studies are needed to elucidate the mechanisms of action
Summary
Different types of injury (ischemic, toxic, oxidative stress, and so on) may induce acute liver damage, which can elicit tissue inflammation. Inflammation, in turn, may contribute to further injury. When the injury or the inflammation persists, liver fibrosis may develop, eventually leading to end-stage liver disease, cirrhosis, and hepatocellular carcinoma. Liver transplantation is the standard therapy for end-stage liver disease, its use is limited by insufficient availability of organs as well as by medical (immunosuppressive therapies) and financial considerations. To establish new anti-fibrotic and anti-inflammatory therapeutic strategies is one of the major clinical options to avoid transplantation. Preclinical studies have suggested that stem cells and their bio-products, in particular stem cell-derived extracellular vesicles (EVs), may represent a therapeutic option to treat or to alleviate liver fibrosis and inflammation
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