Extracellular Vesicle exchange is favored by cell proximity

Abstract

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.

Impacts of tissue context on extracellular vesicles‐mediated cancer–host cell communications

“…reported an interesting observation in their preprint that cancer cells with EV labels cocultured in 2D monolayer transferred EVs only to the proximal cells, mostly within. 38 Culture with agitation did not increase EV transfer in distant orientation. Their observation indicates that EV transfer is limited even in 2D culture.…”

“…which will also limit the distance of EV dissemination.Recently, Colombo et al reported an interesting observation in their preprint that cancer cells with EV labels cocultured in 2D monolayer transferred EVs only to the proximal cells, mostly within 38. Culture with agitation did not increase EV transfer in distant orientation.…”

Defining the Role of the miR-145—KLF4—αSMA Axis in Mitral Valvular Interstitial Cell Activation in Myxomatous Mitral Valve Prolapse Using the Canine Model

“…The increase in miR-145 was found not only in VICs harvested from MVP-affected valves but also in their associated sEV. As sEV can be taken up by neighboring cells for local cell-to-cell communication [28], the content of the sEV produced by myofibroblastic VICs can promote phenotypic transition and activation of neighboring cells and potentially exacerbate the extent of valvular pathology as activated myofibroblastic VICs contributes to the remodeling of the extracellular matrix. This important finding resonates with other recent investigations that demonstrate the importance of local (paracrine) sEV-mediated signaling in cardiac fibrosis [29] or cancer [28].…”

“…As sEV can be taken up by neighboring cells for local cell-to-cell communication [28], the content of the sEV produced by myofibroblastic VICs can promote phenotypic transition and activation of neighboring cells and potentially exacerbate the extent of valvular pathology as activated myofibroblastic VICs contributes to the remodeling of the extracellular matrix. This important finding resonates with other recent investigations that demonstrate the importance of local (paracrine) sEV-mediated signaling in cardiac fibrosis [29] or cancer [28]. sEV ncRNA content may also serve as biomarkers for disease progression; however, as our previous work in plasma sEV has shown, attempts to dissect signals only from the mitral valve may be difficult as overall systemic changes such as in heart failure will also contribute to the overall circulating sEV ncRNA content.…”

A case for the study of native extracellular vesicles

“…As a consequence, only recipient cells that bind nEVs in high numbers can be detected and isolated for profiling studies ( 15 , 20 ). Remote EV-cell communications are much harder to identify as the amount of nEVs exponentially decreases with distance from EV donor cells ( 21 ). Therefore, defining the impact of nEVs on the full repertoire of local and distant recipient cells is still an unmet challenge that requires the application of paradigm-shifting technologies ( 22 ).…”