TABLE 1.
Summary of studies which reported the role of extracellular vesicles in the treatment of liver disorders.
| Cell origin | Type of secreted vesicle | Disease | Target cells or tissues | Molecular mechanism | Biological effect and therapeutic applications | References |
| CP-MSCs | Exosome | liver fibrosis | Hepatocytes | microRNA-125b | Increase liver Regeneration by inhibition of hedgehog (Hh) signal | Hyun et al., 2015 |
| βMSCs | Exosome | CLP | Hepatocytes | miR-146a | Diminish liver damage and decrease mortality | Song et al., 2017 |
| BM-MSCs | Conditioned medium | Acute liver failure | Th1 and Th17 cells | IL-10; CXCR3 and CCR5 | Decrease invasion in the injured liver | Van Poll et al., 2008 |
| HA-MSCs | EVs | Acute liver failure | Hepatocytes | lncRNA H19 | Increase hepatocytes proliferation and decrease mortality | Jin et al., 2018 |
| HA-MSCs | Exosome | Acute liver failure | Macrophages | miR-17 | Suppress the activation of NLRP3 inflammatory bodies | Liu et al., 2018 |
| UC-MSCs | Exosome | Liver fibrosis | Hepatic cells | TGF-β/Smad2 | Decrease collagen production | Li T. et al., 2013 |
| hUCMSCs | Exosome | Acute liver failure | Hepatocytes | miR-299-3p | Decrease inflammation through suppression of NLRP3-related pathways | Zhang et al., 2020 |
| MSC | Exosome | HBV | Macrophage | HBV-miR-3/SOCS5/STAT1 | Macrophage M1 polarization and IL-6 secretion | Zhao X. et al., 2020 |
| MSC | Exosome | HBV | Macrophage | HBV-infected hepatocyte exosomes/MyD88, TICAM-1, and MAVS | Enhance immune response in the host | Kouwaki et al., 2016 |
| BM-MSCs | Conditioned medium/Exosome | Acute liver failure | Hepatocytes | IDO-1/KYN; HGF; FLP1; IL-6/gp130; Bcl-xL; Cyclin D1 | Increase proliferation and suppress apoptosis | Xagorari et al., 2013; Gazdic et al., 2018; Milosavljevic et al., 2018 |
| hUCMSCs | Exosome | Liver failure | Hepatocytes | GPX1 | Decrease oxidative stress and apoptosis | Yan et al., 2017 |
| BM- MSCs | Exosome | Autoimmune hepatitis | Hepatocytes | miR-223 | ALT and AST levels were diminished and apoptosis was inhibited. | Chen et al., 2018 |
| BM-MSCs | Conditioned medium | Acute liver failure | Natural killer T cells | IDO-1/KYN | Decrease inflammatory Cytokines secretion and decrease cytotoxicity | Xagorari et al., 2013; Gazdic et al., 2018; Milosavljevic et al., 2018 |
| MSC | Exosome | NAFLD | Macrophage | miR122-5p/lysosome | M1 polarization | Zhao Z. et al., 2020 |
| MSC | Exosome | Hepatocellular carcinoma | Macrophage | lncRNA TUC339/Toll-like receptor signaling and FcgR-mediated phagocytosis | Decrease in pro-inflammatory cytokine secretion and enhance the phagocytosis | Li X. et al., 2018 |
| MSC | Exosome | Hepatocellular carcinoma | Macrophage | Exo-con/STAT3 | Enhance cytokine secretion in macrophages | Cheng et al., 2017 |
| BM-MSCs | Exosome | Acute liver failure/liver fibrosis | Leukocyte | IDO-1/KYN; TGF-; IL-10 | Suppressed activation of the inflammasome | Lou et al., 2017a; Milosavljevic et al., 2017 |
| MSC | Exosome | Alcoholic liver disease | Macrophage | miR-27A/CD206 on monocytes | M2 polarization | Saha et al., 2016 |
| MSC | Exosome | Alcoholic liver disease | Macrophage | CD40L/Caspase-3 | M1 polarization | Eguchi et al., 2016 |
| MSC | Exosome | Alcoholic liver disease | Monocytes | miR-122/HO-1 | Increase sensitivity of monocytes to LPS | Fairclough et al., 2014 |
| MSC | Exosome | Alcoholic liver disease | Kupffer cells | Mitochondrial double-stranded RNA/TLR3 in Kupffer cells | Increase in IL-1b and IL–17A levels | Lee et al., 2020 |
| MSC | Exosome | NAFLD | Macrophage | Hepatocyte-derived EV/DR5/Caspase/ROCK1 | Enhance macrophage pro-inflammatory | Hirsova et al., 2016 |
| MSC | Exosome | NAFLD | Monocytes | Lipotoxic EVs/ITGb1 | Increase monocyte adhesion and inflammatory response | Gallina et al., 2019 |
| MSC | Exosome | Hepatocellular carcinoma | Macrophage | miR-23a-3p/PTEN/AKT | Inhibition of T-cell function | Li T. et al., 2013 |
| MSC | Exosome | Hepatocellular carcinoma | Hepatocytes | miR-142-3p/RAC1 | supress hepatocellular carcinoma cell migration and invasion | Zhang et al., 2014 |
| UC- MSCs | EVs | Hepatitis | Liver cells | miR-let-7f, miR-145, miR-199a, miR-221 | Protect liver cells against HCV | Qian et al., 2016 |
| BM-MSCs | Exosome | Liver injury | – | Cationized pullulan | Anti-inflammatory effect | Tamura et al., 2017 |
| MenSCs | Exosome | Fulminant liver failure | Hepatocytes | ICAM-1, osteoprotegerin, angiogenin-2, | Decrease mortality and inhibits apoptosis | Yang et al., 2017a |
| HA-MSCs | Exosome | liver fibrosis | Hepatocytes | miR-122 | Decrease collagen deposition | Lou et al., 2017b |
| MSC | Exosome | HCV | Macrophage | Anti-HCV miRNA-29/TLR3-activated macrophages | Decrease HCV replication | Zhou et al., 2016 |
| MSC | Exosome | HCV | Monocytes | Exosome-packaged HCV/TLR7/8 | Differentiation of monocytes into macrophages | Saha et al., 2017 |
| MSC | Exosome | Alcoholic liver disease | Macrophage | miR-155/Hsp90 | Enhance in inflammatory macrophages | Babuta et al., 2019 |
| MSC | Exosome | NAFLD | Macrophage | mi R-192-5p/Rictor/Akt/FoxO1 | M1 polarization | Liu et al., 2020 |
BM-MSCs, bone marrow mesenchymal stem cells; UC-MSCs, umbilical cord mesenchymal stem cells; KYN, Kynurenine; CCR5, C-C chemokine receptor type 5; TGF-β, transforming growth factor beta; IDO-1, indoleamine 2,3 dioxygenase-1; HA-MSC, human adipose-derived mesenchymal stem cells; MenSC-Exos, human menstrual blood stem cell-derived exosomes; hUCMSC-Exos, Human umbilical cord mesenchymal stem cell-derived exosomes; CP-MSC, chorionic plate-derived mesenchymal stem cells; βMSC, MSC pre-treated with IL-1β; CLP, Puncture induced sepsis; NAFLD, Nonalcoholic fatty liver disease.