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.
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.
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.
Conversely, pharmacological inhibition of EV release, through Calix[6]arene, can slow down progression of experimental pancreatic cancer.
[4] 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.
[5] Ultracentrifuged pellets from blood plasma were reported to have procoagulant properties by Erwin Chargaff and Randolph West in 1946.
[7] Around the same time, H. Clarke Anderson and Ermanno Bonucci separately described the calcifying properties of EVs in bone matrix.
[9] This electron microscopy study of the flagellate freshwater alga 'Ochromonas danica' reported release of EVs from membranes including those of flagella.
EVs were also described in bovine serum and cell culture conditioned medium[14][13] with distinctions made between "vesicles of the multivesicular body" and "microvesicles.
Diverse EV subtypes have been proposed, with names such as ectosomes, microvesicles, microparticles, exosomes, oncosomes, apoptotic bodies, and more.
Because of the bewildering and sometimes contradictory definitions of different EV subtypes, the current scientific consensus is that "extracellular vesicle" and variations thereon are the preferred nomenclature unless specific biogenetic origin can be demonstrated.
Technically, the platelets of certain vertebrates (which bud from megakaryocytes), as well as red blood cells (e.g., of adult humans) also fulfill the consensus definition of EVs.
[citation needed] Exosome biogenesis begins with pinching off of endosomal invaginations into the multivesicular body (MVB), forming intraluminal vesicles (ILVs).
[51] Exophers are a class of large EV, approximately four microns in diameter, observed in model organisms ranging from Caenorhabditis elegans[52] to mice.
[52] Migrasomes are large membrane-bound EVs, ranging from 0.5 to 3 microns in diameter, that form at the ends of retraction fibers left behind when cells migrate in a process termed "migracytosis."
[54] Damaged mitochondria can be expelled from migrating cells inside of migrasomes, suggesting a functional role for this EV in mitochondrial homeostasis.
Molecular "fingerprints" of populations can be obtained by "omics" technologies like proteomics, lipidomics, and RNomics, or by techniques like Raman spectroscopy.
The challenge for any putative single-particle method is to identify the individual EV as a single, lipid-bilayer particle, and to provide additional information such as size, surface proteins, or nucleic acid content.
Some technologies allow the study of individual EVs without extensive prior separation from a biological matrix: to give a few examples, electron microscopy and flow cytometry.
To demonstrate the presence of EVs in a preparation, as well as the relative depletion of non-EV particles or molecules, EV-enriched 'and' -depleted markers are necessary:[65] For example, the MISEV2018 guidelines recommend: Usually, but not necessarily, the EV-enriched or -depleted markers are proteins that can be detected by Western blot, flow cytometry, ELISA, mass spectrometry, or other widely-available methods.
Extracellular vesicle secretion is generally believed to increase with age due to DNA or mitochondrial damage and lipid peroxidation.
It has thus been demonstrated that EVs released by hepatocytes under NAFLD conditions cause vascular endothelial inflammation and promote atherosclerosis.
PS is an anionic phospholipid and PS+ EVs therefore provide a negatively charged surface which may facilitate formation of coagulation complexes.
[76][77] In vitro studies of Alzheimer's disease have shown that astrocytes that accumulate amyloid beta release EVs that cause neuronal apoptosis.
[81] It has been suggested that EVs carrying nucleic acid cargo could serve as biomarkers for disease, especially in neurological disorders where it is difficult to assess the underlying pathology directly.
Exosome Diagnostic (Cambridge, MA, USA), for example, has a patent for detecting neurodegenerative diseases and brain injury based on the measure of RNA-s (mRNA, miRNA, siRNA, or shRNA) associated with CSF-derived EVs.