Microneedle Delivery of Small Extracellular Vesicles From Young Blood to Treat Endothelial Senescence.

Abstract

Circulating extracellular vesicles (EVs) play a crucial role in mediating communication between different cell populations and organs, significantly influencing inflammation and vascular diseases. To evaluate the role of EVs in regulating senescence, small EVs isolated from umbilical cord plasma (young sEVs, Y-sEVs) are compared with those from the plasma of elderly individuals (old sEVs, O-sEVs, >70 years old) to identify key cargo components. To investigate their effects on senescence, Y-sEVs or O-sEVs are administered to aged mice using transdermal microneedle patches, enabling sustained EV release into the circulation. Doxorubicin is administered to induce enhanced endothelial senescence in aged mice (22-24 months old). Single-cell RNA sequencing revealed that Y-sEV treatment downregulated senescence-related genes in endothelial cells decreased the proportion of activated fibroblasts in the heart, and reduced disease-associated microglia in the brain. Delivery of Y-sEVs via microneedle patches preserved endothelial cell function, and mitigated inflammation and senescence, whereas O-sEVs exacerbated endothelial dysfunction.