Extracellular vesicle

Extracellular vesicles (EVs) are lipid bilayer-delimited particles that are naturally released from almost all types of cells but, unlike a cell, cannot replicate^[1]. EVs range in diameter from near the size of the smallest physically possible unilamellar liposome (around 20-30 nanometers) to as large as 10 microns or more, although the vast majority of EVs are smaller than 200 nm. EVs can be divided according to size and synthesis route into exosomes, microvesicles and apoptotic bodies.^[2][3] The composition of EVs varies depending on their parent cells, encompassing proteins (e.g., adhesion molecules, cytoskeletons, cytokines, ribosomal proteins, growth factors, and metabolic enzymes), lipids (including cholesterol, lipid rafts, and ceramides), nucleic acids (such as DNA, mRNA, and miRNA), metabolites, and even organelles.^[4][5] Most cells that have been studied to date are thought to release EVs, including some archaeal, bacterial, fungal, and plant cells that are surrounded by cell walls. A wide variety of EV subtypes have been proposed, defined variously by size, biogenesis pathway, cargo, cellular source, and function, leading to a historically heterogenous nomenclature including terms like exosomes and ectosomes.

Numerous functions of EVs have been established or postulated. The first evidence for the existence of EVs was enabled by the ultracentrifuge, the electron microscope, and functional studies of coagulation in the mid-20th century. A sharp increase in interest in EVs occurred in the first decade of the 21st century following the discovery that EVs could transfer nucleic acids such as RNA from cell to cell. Associated with EVs from certain cells or tissues, nucleic acids could be easily amplified as markers of disease and also potentially traced back to a cell of origin, such as a tumor cell. When EVs are taken up by other cells, they may alter the behaviour of the recipient cell, for instance EVs released by colorectal cancer cells increase migration of fibroblasts and thus EVs are of importance in forming tumour landscapes.^[6] This discovery also implied that EVs could be used for therapeutic purposes, such as delivering nucleic acids or other cargo to diseased tissue. Conversely, pharmacological inhibition of EV release, through Calix[6]arene, can slow down progression of experimental pancreatic cancer.^[7] The growing interest in EVs as a nexus for therapeutic intervention was paralleled by formation of companies and funding programs focused on development of EVs as biomarkers or therapies of disease, the founding of an International Society for Extracellular Vesicles (ISEV), and establishment of a scientific journal devoted to the field, the Journal of Extracellular Vesicles.