Table 3 Studies demonstrating the MSC-EV-mediated transfer of miRNAs in animal models
References | Disease model | Treatment with MSC-EVs or MSCs, dose, duration, and route | Major findings | miRNA transferred | Target proteins |
|---|---|---|---|---|---|
Collino et al. 2015 [48] | Mouse, rhabdomyolysis-induced acute kidney injury | MSC-EVs with Drosha knockdown or control, 2.2 × 108 EV particles, on day 3 of injury, tail veil | Drosha knockdown blocked morphologic and functional recovery in acute kidney injury | Reduction in all miRNAs in EVs from Drosha knockdown | ND |
Wang et al. 2016 [50] | Mouse, renal fibrosis from ureteral obstruction | MSCs with miR-let7c overexpression, 1 × 106 cells, 0 h after obstruction, intravenous | Attenuated kidney injury and fibrosis | miR-let7c | TGF-β receptor 1 |
Gu et al. 2016 [51] | Rat, renal ischemia-reperfusion injury | MSC-EVs, 100 μg, 0 h after reperfusion, intravenous | Protect the kidney from the injury by inhibition of mitochondrial fission | miR-30 | DRP1 |
Feng et al. 2014 [52] | Mouse, MI | MSC-EVs from ischemic precondition, 1 μg, 0 h after ischemia, intramyocardium | Reduced infarct size | miR-22 | Methyl-CpG-binding protein 2 |
Yu et al. 2015 [53] | Rat, MI | EVs from MSCs with GATA-4 overexpression, harvested from 4 × 106 MSCs, 0 h after ischemia, intramyocardium | Reduced infarct size, promoted cardiac function recovery | miR-19a | PTEN |
Wang et al. 2015 [54] | Mouse, sepsis-induced cardiac dysfunction | MSC-EVs, 2 μg/g body weight, 1 h after cecal ligation and puncture model, intravenous | Protection against cardiac dysfunction, apoptosis, and inflammatory response | miR-223 | Sema3A and Stat3 |
Lou et al. 2015 [56] | Nude mouse, hepatocellular carcinoma | MSC-EVs, 50 μg, intra-tumor injection | Increased the antitumor efficacy of sorafenib on hepatocellular carcinoma | miR-122 | Cyclin G1 and IGF1R |
Lou et al. 2017 [57] | Mouse, CCl4-induced liver fibrosis | MSCs with miR-122 overexpression, 1 × 105 cells, 1 day after the fourth injection of CCl4, tail vein | Alleviated liver fibrosis and collagen deposition | miR-122 | Cyclin G1, IGF1R, and P4HA1 |
Chen et al. 2018 [58] | Mouse, experimental autoimmune hepatitis | EVs from MSCs with miR-223 overexpression; dose not shown; on days 21, 28, and 35 of 42-day experiment; intraperitoneally | Reduced inflammation and reversed liver injury | miR-223 | NLRP3 |
Qu et al. 2017 [59] | Mouse, CCl4-induced liver fibrosis | EVs from MSCs with miR-181 overexpression, 40 μg, twice weekly for 8 weeks, intrasplenic injection | Inhibited liver fibrosis and activated autophagy | miR-181 | Bcl-2 and Stat3 |
Xin et al. 2012 [60] | Rat, stroke from middle cerebral artery occlusion | MSCs, 3 × 106 cells, 24 h postischemia, tail vein | MSCs increased miR-133b level in the brain, MSC-EVs elevated neurite outgrowth in vitro | miR-133 | RhoA (candidate) |
Xin et al. 2013 [61] | Rat, stroke from middle cerebral artery occlusion | MSCs with miR-133 overexpression or knockdown, 3 × 106 cells, 24 h postischemia, tail vein | miR-133 enhanced axonal plasticity and neurite remodeling | miR-133 | Connective tissue growth factor and RhoA |
Xin et al. 2017 [62] | Rat, stroke from middle cerebral artery occlusion | EVs from MSCs with miR-17-92 cluster expression, 100 μg, 24 h postischemia, intravenous | Increased neural plasticity and functional recovery | miR-17-92 cluster | PTEN |