Engineering Stem Cell-Derived Small Extracellular Vesicles for Delivery of miRNA in Cardiac Repair
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초록
내용
The cell membrane nanovesicles, particularly small extracellular vesicles (sEVs) also known as exosomes, play a crucial role in intercellular communication by transporting cargo. sEVs play a crucial role in stem cell therapy, as the inhibition of their synthesis negates the therapeutic effect following cardiac injury. sEVs have been identified as crucial biomarkers that reflect the cellular environment, and increasing evidence suggests that the microRNAs (miRNAs) present within sEVs play a critical role in regulating cellular functions, including inflammation, cell recruitment, and proliferation. However, miRNA content in sEVs is highly heterogeneous, and not all miRNAs present within sEVs exert a beneficial effect. Computational methods have revealed co-varying cellular and EV RNAs in relation to donor age, and these co-varying RNAs have been shown to regulate cellular functions, including angiogenesis, inflammation, fibrosis, and mesenchymal stromal cell migration. In this study, specific miRNAs highly connected to cardiac disease propagation and repair were identified through computational methods, and their content was modified in sEVs derived from cardiac progenitor cells. The resulting EVs, either devoid of deleterious miRNA or containing reparative miRNAs identified through computational methods, were tested in a rat model of cardiac ischemia-reperfusion. The results suggest that engineered sEVs represent a promising therapeutic strategy for the treatment of cardiovascular diseases.