Extracellular vesicles: A complex array of particles involved in cell-to-cell communication for tissue homeostasis

Communication between cells is an inescapable feature of every multicellular organism, from the coordination of development during embryogenesis to the maintenance of homeostasis throughout adulthood. Extracellular vesicles (EVs) are new and central players in intercellular communication processes, by carrying multiple signals at once and acting in concert with well-described soluble effectors released in the environment. These membrane-enclosed particles are released by all cells in their environment. Their lipid bilayer protects their internal content while exposing surface determinants, allowing EVs to interact with target cells and/or surrounding extracellular matrix. EVs can also escape to blood or lymph circulation and reach further away organs. By carrying multiple signals, locally or at a distance, EVs are increasingly considered as players in the coordination of physiological processes within and across tissues. Here, we briefly summarize the many studies describing physiological functions of EVs, and discuss their actual demonstration in vivo. In addition, we discuss this knowledge in light of our current understanding on the heterogeneity of EVs, the complex composition of EV-containing preparations and the consequences to unravel the specific activities of EVs, including subtypes of EVs such as exosomes, and of other extracellular particles (EPs).