Extracellular Vesicles—Is There a Consensus Definition?
Extracellular vesicles (EVs) are a family of cell-derived fragments or vesicles generated by cell membrane shedding or storage vesicle exocytosis. This occurs following biological processes such as cell activation and modes of cell death such as necrosis and apoptosis. Major sources or contributors of EVs in the blood are platelets, leukocytes and endothelial cells. Secretory glands comprised of epithelial cells also are a major source of EVs but their contribution to the EV pool in blood is unclear. Several types of EVs are described throughout the literature; they are categorized according to their size, contents and mechanism by which they are released. For example, exosomes (30–100 nm) are EVs of cytoplasmic origin, released or exocytosed into the extracellular environment upon fusion of multivesicular bodies with the plasma membrane. Microparticles (MPs), also known as microvesicles, are larger than exosomes measuring 100–1000 nm, and are the primarily result of membrane blebs released from the surface of cells. Lastly, apoptotic bodies (APBs) are larger cell-derived vesicles, measuring up to 4000 nm and are eponymously generated during cell apoptosis. Given their origin and release from cells, EVs are commonly endowed with a portion of membrane proteins, and in some APBs, genetic remnants of the parent cell. It is now generally accepted that EVs, such as platelet MPs, play a significant role in modulating normal physiological processes such as coagulation via expression of multifunctional cellular signaling proteins such as tissue factor. However, despite observations of elevated EVs in cancer patient plasmas and other diseases, it is still undetermined whether they originate from tumors, whether they serve as a rich reservoir of biomarkers for disease detection and the role they play in disease progression.