Anex vivomodel of interactions between extracellular vesicles and peripheral mononuclear blood cells in whole blood

Abstract

AbstractExtracellular vesicles (EVs) can be loaded with therapeutic cargo and engineered for retention by specific body sites; therefore, they have great potential for targeted delivery of biomolecules to treat diseases. However, the pharmacokinetics and biodistribution of EVs in large animals remain relatively unknown, especially in primates. We recently reported that when cell culture-derived EVs are administered intravenously toMacaca nemestrina(pig-tailed macaques), they differentially associate with specific subsets of peripheral blood mononuclear cells (PBMCs). More than 60% of CD20+B cells were observed to associate with EVs for up to 1 hr post-intravenous administration. To investigate these associations further, we developed anex vivomodel of whole blood collected from healthy pig-tailed macaques. Using thisex vivosystem, we found that labeled EVs preferentially associate with B cells in whole blood at levels similar to those detectedin vivo. This study demonstrates thatex vivoblood can be used to study EV-blood cell interactions.