Table 4 miRNA-engineerd EVs as an advanced drug delivery system in Cardiovascular Disorders
Therapeutic miRNA | miRNA Enrichment | Incorporation method | Source of EVs | Target | in vitro Cell Lines Utilized | in vitro Findings | in vivo Model | in vivo Findings | Source |
|---|---|---|---|---|---|---|---|---|---|
miR-125b | Endogenous | Lipofectamine™ Transfection | Rat BM-MSCs | Ischemia reperfusion (I/R) injury model | Rat I/R myocardium cells | Restoration of cell viability coupled with a decease in the apoptotic ratio. Additionally, the levels of IL-1b, IL-6 and TNF-a proteins were significantly reduced, indicating reduced cellular inflammation | Rat Ischemia reperfusion (I/R) model | Restored cardiac function as seen through significantly lower infarct size, reduced ratio of inflammatory cells, and restored left ventricular function | Chen, Qi, et al. [181] |
miR-494-3p | Endogenous | RiboFECTTM Transfection | Murine bone marrow-derived dendritic cells | Murine myocardial infarction | Cardiac microvascular endothelial cells | Enhanced tube formation | Murine myocardial infarction model | Increased VEGF expression and a significant increase in the mean number of vessels in the myocardium | Liu, Haibo, et al. [182] |
miR-210 | Endogenous | Transfection | Human Adipose Derived Stem Cells | Ischemia heart disease | Hypoxic endothelial cells and H9C2 cardiomyocyte cells | Inhibition of EFNA3 in endothelial cells and a significant increase in VEGF expression combined with an increase in viability for cardiomyocyte cells | Rat I/R injury model | Significant increase in cardiac function and no significant changes in fibrotic area ratio | Song, Byeong-Wook, et al. [183] |
miR-144-3p | Exogenous | Exo-Fect™ Transfection | HEK293 cells | Murine myocardial infarction | H9C2 rat myoblast cells | Increased cell viability, decreased lactate dehydrogenase release, and decreased cellular apoptosis after H2O2-induced cellular injury | Murine myocardial infarction model | Reduction of infarct size, significantly reduced cell death, and no systemic toxicity | Kang, Ji-Young, et al. [184] |
miR-126 | Endogenous | Lipofectamine™ Transfection | Human BM-MSCs | Nonspecific angiogenesis | HUVECs | Enhanced proliferation, migration, and tube formation | Murine full-thickness cutaneous wound model | Significantly increased wound closure rate, reduction of scar formation, and enhancement of angiogenesis | Zhang, Lei, et al. [185] |
miR-186 | Endogenous | Lipofectamine™ Transfection | Human BM-MSCs | Idiopathic pulmonary fibrosis | LL29 human lung fibroblasts | Suppression of lung fibroblast activation and reduced fibroblast viability and invasion | Murine pulmonary fibrosis model | Reduced expression of myofibroblastic markers, reduction in collagen fibers, impaired fibroblast activation, and suppression of idiopathic pulmonary fibrosis | Zhou, Jing, et al. [186] |
miR-146a, miR-370, miR-126a | Endogenous | Trans-IT TKO (Mirus) | NHDF-EVs | Ischemic heart disease | C57BL/6 mouse primary neonatal cardiomyocytes | Therapeutic miRNA cluster acts synergistically to reduce cardiomyocyte apoptosis | N/A | N/A | Euscher LM, et al. [187] |