*3.1. EVs and Their Origin*

EVs are small, membrane-bound vehicles of intercellular communication that carry various types of cellular information throughout the body. The role of EVs in cell–cell interactions is rather complicated; thus, EVs may influence the pathophysiology of recipient cells in either positive or negative ways [80]. EVs comprise a heterogenous group and are therefore classified into three major categories based on their biogenesis pathway: exosomes, micro-vesicles, and apoptotic bodies [29]. Exosomes (<200 nm), which originate from endosomal compartments, are secreted from cells when micro-vesicular bodies (MVBs) fuse with the plasma membrane, whereas micro-vesicles (50–1000 nm) are routinely shed from cell membranes, and apoptotic bodies (50–5000 nm) are released during membrane blebbing upon programed cell death [29]. Due to overlaps in size, composition, and marker proteins, exosome characterization has proved to be challenging for researchers [30]. Therefore, we will exclusively refer to "EVs", even when published data refers to "exosomes".
