The microenvironment-a general hypothesis on the homeostatic function of extracellular vesicles

Extracellular vesicles (EVs), exosomes and microvesicles, is a burgeoning field of biological and biomedical research that may change our understanding of cell communication in plants and animals while holding great promise for the diagnosis of disease and the development of therapeutics. However, the challenge remains to develop a general hypothesis about the role of EVs in physiological homeostasis and pathobiology across kingdoms. While they can act systemically, EVs are often seen to operate locally within a microenvironment. This microenvironment is built as a collection of microunits comprised of cells that interact with each other via EV exchange, EV signaling, EV seeding, and EV disposal. We propose that microunits are part of a larger matrix at the tissue level that collectively communicates with the surrounding environment, including other end-organ systems. Herein, we offer a working model that encompasses the various facets of EV function in the context of the cell biology and physiology of multicellular organisms.