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Knockdown of miR-192 and miR-432 in progenitor cell-derived small extracellular vesicles enhances tissue repair in myocardial infarction

ABSTRACT: Small extracellular vesicles (sEVs) play a critical role in cardiac cell therapy by delivering molecular cargo and mediating cellular signaling. Among sEV cargo molecule types, microRNA (miRNA) is particularly potent and highly heterogenous. However, not all miRNAs in sEV are beneficial. Two previous studies utilizing computational modeling identified miR-192-5p and miR-432-5p as potentially deleterious in cardiac function and repair. Here, we show that knocking down miR-192-5p and miR-432-5p in cardiac c-kit+ cell-derived sEVs enhances the therapeutic capabilities of sEVs in vitro and in a rat in vivo model of cardiac ischemia reperfusion. miR-192-5p and miR-432-5p depleted CPC-sEVs enhance cardiac function by reducing fibrosis, enhancing mesenchymal stromal cell-like cell mobilization, and inducing macrophage polarization to the M2 phenotype. Knocking down deleterious miRNAs from sEV could be a promising therapeutic strategy for treatment of chronic myocardial infarction.

ORGANISM(S): Rattus norvegicus Homo sapiens

PROVIDER: GSE196469 | GEO | 2022/12/31

REPOSITORIES: GEO

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Small extracellular vesicles secreted from senescent cells promote cancer cell proliferation through EphA2.

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MOLECULAR PROFILING OF DECOMPENSATED CIRRHOSIS BY A NOVEL microRNA SIGNATURE

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2021-02-10 | GSE150867 | GEO

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2023-10-31 | GSE167961 | GEO

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