Extracellular Vesicle exchange is favored by cell proximity

Extracellular vesicles (EVs) are biological nanovectors that retain information of the cell of origin and convey signals to recipient cells. Therefore, EVs are ideal platforms for the development of diagnostic tools and of bio-inspired drug delivery technologies. However, the dynamics of EV distribution in physiological conditions are still underexplored. Using an elegant series of experiments, including quantitative assays to define EV transfer and five dimension live cell imaging, we observe the release and internalization of EVs in real time and we demonstrate that EVs are mainly exchanged at the cell-cell interface. These observations prompt paradigm shifting consequences: first, EVs are mostly short-range intercellular vectors that influence adjacent cells; second, our data explain why increases in the internal pressure and permeability of the parenchyma, two hallmarks of inflammation and cancer, can facilitate EV escape from the damaged tissue. In conclusion, we provide experimental evidence supporting why EVs have great potential for the implementation of specific and sensitive liquid biopsy tests.