Targeting the heart: Extracellular vesicles and beyond

Abstract

Extracellular vesicles are cell-derived tiny particles that naturally transport different molecules including RNA between cells, inducing a response in the receiving cell. This thesis focused on the use of extracellular vesicles for cardiac applications by manipulating their content and favouring their accumulation in the heart. This research showed that these vesicles can be enriched with long non-coding RNAs, molecules known to play important roles in the heart. They were further shown to transport them to different cells that are usually present in the heart. However, once intravenously injected in animals, these vesicles do not accumulate in the heart, limiting their use for cardiac therapies. Finally, we proposed the use of a transporter that would degrade in response to an external stimulus and locally release the vesicles loaded on it. With this non-invasive system we were able to double the amount of vesicles that reach and accumulate in the heart, paving the way for improved vesicle-based treatments.