Multiplexed targeting of miRNA-210 in stem cell-derived extracellular vesicles promotes selective regeneration in ischemic hearts

Extracellular vesicles (EVs) are cell derivatives containing diverse cellular molecules, have various physiological properties and are also present in stem cells used for regenerative therapy. We selected a “multiplexed target” that demonstrates multiple effects on various cardiovascular cells, while functioning as a cargo of EVs. We screened various microRNAs (miRs) and identified miR-210 as a candidate target for survival and angiogenic function. We confirmed the cellular and biological functions of EV-210 (EVs derived from ASC miR-210 ) secreted from adipose-derived stem cells (ASCs) transfected with miR-210 (ASC miR-210 ). Under hypoxic conditions, we observed that ASC miR-210 inhibits apoptosis by modulating protein tyrosine phosphatase 1B (PTP1B) and death-associated protein kinase 1 (DAPK1). In hypoxic endothelial cells, EV-210 exerted its angiogenic capacity by inhibiting Ephrin A (EFNA3). Furthermore, EV-210 enhanced cell survival under the control of PTP1B and induced antiapoptotic effects in hypoxic H9c2 cells. In cardiac fibroblasts, the fibrotic ratio was reduced after exposure to EV-210, but EVs derived from ASC miR-210 did not communicate with fibroblasts. Finally, we observed the functional restoration of the ischemia/reperfusion-injured heart by maintaining the intercommunication of EVs and cardiovascular cells derived from ASC miR-210 . These results suggest that the multiplexed target with ASC miR-210 is a useful tool for cardiovascular regeneration. Heart disease: Boosting microRNA activity may restore heart function A therapy designed to enhance the activity of a small regulatory RNA molecule could prompt the restoration of cellular communication and improve heart function during heart disease. Heart cells struggle to function and regenerate under the reduced oxygen conditions caused by narrowed or blocked blood vessels. Stem cell-derived therapies may restore damaged heart tissues, and can be designed to secrete specific factors that boost regeneration. To identify factors that may improve heart recovery chances, Woochul Chang at Pusan National University, Busan, Korea and co-workers examined stem cell-derived extracellular vesicles (EVs), cellular membrane sacs that carry proteins and RNAs to surrounding tissues and boost intercellular communication. The team identified microRNA-210 as a key factor that inhibits heart cell death, reduces fibrosis, and enhances regeneration of heart cell populations. EVs secreting microRNA-210 may pro