High-efficiency engineering of highly active extracellular vesicles for myocardial infarction therapy

Extracellular vesicles have shown good potential in disease treatments including ischemic injury such as myocardial infarction. However, the efficient production of highly active extracellular vesicles is one of the critical limitations for their clinical applications. Researchers at Southern Medical University demonstrate a biomaterial-based approach to prepare high amounts of extracellular vesicles with high bioactivity from endothelial progenitor cells (EPCs) by stimulation with silicate ions derived from bioactive silicate ceramics. The researchers further show that hydrogel microspheres containing engineered extracellular vesicles are highly effective in the treatment of myocardial infarction in male mice by significantly enhancing angiogenesis. This therapeutic effect is attributed to significantly enhanced revascularization by the high content of miR-126a-3p and angiogenic factors such as VEGF and SDF-1, CXCR4 and eNOS in engineered extracellular vesicles, which not only activate endothelial cells but also recruit EPCs from the circulatory system.

High-efficiency engineering of highly active extracellular vesicles by the treatment of endothelial progenitor cells (EPCs) with silicate ions derived from bioactive ceramics for myocardial infarction therapy through enhancement of revascularization of infarcted tissues

Fig. 1

a EPCs were induced by calcium silicate (CS) ions to secrete highly active extracellular vesicles (CS-EPC-EV), and microspheres loaded with highly active extracellular vesicles (microsphere+CS-EPC-EVs) were prepared by microfluidic technology. b In situ injection of microsphere+CS-EPC-EVs at the site of myocardial infarction in mice to repair myocardial injury. c The mechanism of microspheres for the treatment of myocardial infarction. On the one hand, the extracellular vesicles in the microspheres inhibit apoptosis and promote proliferation, migration and angiogenesis of surviving endothelial cells (ECs) in the infarct border zone of myocardial infarction. On the other hand, extracellular vesicles recruit EPCs generated in the bone marrow from the circulatory system to the infarct border zone, which integrate themselves into damaged blood vessels through proliferation, migration, and differentiation, thereby promoting angiogenesis.

Yu B, Li H, Zhang Z et al. (2023) Extracellular vesicles engineering by silicates-activated endothelial progenitor cells for myocardial infarction treatment in male mice. Nat Commun [Epub ahead of print]. [article]

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