Extracellular vesicle

409:, apoptotic bodies, and more. These EV subtypes have been defined by various, often overlapping, definitions, based mostly on biogenesis (cell pathway, cell or tissue identity, condition of origin). However, EV subtypes may also be defined by size, constituent molecules, function, or method of separation. 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. Subtypes of EVs may be defined by: 630:

preparation cannot be claimed. However, most studies of EVs prior to 2016 did not support claims of the presence of EVs by showing enriched markers, and <5% measured the presence of possible co-isolates/contaminants. Despite the high need, a list of EV contaminants is not yet available to the EV research community. A recent study suggested density-gradient-based EV separation from biofluids as an experimental set-up to compile a list of contaminants for EV, based upon differential analysis of EV-enriched fractions versus soluble protein-enriched fractions. Soluble proteins in blood, the

580:. Total particle counts in a preparation can also be estimated, for example by light-scattering techniques. Each measurement technology may have a specific size range for accurate quantitation, and very small EVs (<100 nm diameter) are not detected by many technologies. Molecular "fingerprints" of populations can be obtained by "omics" technologies like proteomics, lipidomics, and RNomics, or by techniques like 413:"a) physical characteristics of EVs, such as size ("small EVs" (sEVs) and "medium/large EVs" (m/lEVs), with ranges defined, for instance, respectively, <100nm or <200nm , or >200nm ) or density (low, middle, high, with each range defined); b) biochemical composition (CD63+/CD81+- EVs, Annexin A5-stained EVs, etc.); or c) descriptions of conditions or cell of origin (podocyte EVs, hypoxic EVs, 366:

involvement of EVs in cancer progression aroused considerable interest, leading to hypotheses that specific EVs could target specific cells due to "codes" displayed on their surface; create or enhance a metastatic niche; betray the presence of specific cancers; or be used as a therapy to target cancer cells. Meanwhile, strides were made in the understanding of vesicle biogenesis and subtypes.

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chromatography, ultrafiltration, capillary electrophoresis, asymmetric-flow field-flow fractionation, and affinity/immunoaffinity capture methods. Each method has its own recovery and purity outcomes: that is, what percentage of input EVs are obtained, and the ratio of "true" EV components to co-isolates. EV separation can also be influenced by pre-analytical variables.

381:(NIH) announced a program for funding of EV and extracellular RNA studies, the Extracellular RNA Communication Consortium (ERCC), which subsequently invested >USD 100 million in EV research. A second round of funding was announced in 2018. Commercial investment in EV diagnostics and therapeutics also grew during this time. 525:

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." Migrasomes can continue to fill with cytosol and expand even as the originating cell moves away. Migrasomes

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Studies indicate that EVs may have a procoagulant effect in various diseases. EVs can express phosphatidylserine (PS) on their surface. PS is an anionic phospholipid and PS+ EVs therefore provide a negatively charged surface which may facilitate formation of coagulation complexes. Under pathological

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EVs have been implicated in senescence. Extracellular vesicle secretion is generally believed to increase with age due to DNA or mitochondrial damage and lipid peroxidation. It has been demonstrated that exosomes released by senescent cells have a miRNA content that contributes to aging. miRNAs play

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for evaluating EV size, concentration and zeta potential, as well as electron microscopy (no lower bound) and immuno electron microscopy, single-particle interferometric reflectance imaging (down to about 40 nm), and nano-flow cytometry (also to 40 nm). Some technologies allow the study of

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Specialized methods are needed to study EVs at the single particle level. 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. Methods

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Studying EVs and their cargo typically requires separation from a biological matrix (such as a complex fluid or tissue) so that the uniquely EV components can be analyzed. Many approaches have been used, including differential ultracentrifugation, density gradient ultracentrifugation, size exclusion

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cells increase migration of fibroblasts and thus EVs are of importance in forming tumour landscapes. 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,

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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. Assaying for depleted markers is thought to be particularly important, as otherwise the purity of an EV

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Exosome biogenesis begins with pinching off of endosomal invaginations into the multivesicular body (MVB), forming intraluminal vesicles (ILVs). If the MVB fuses with the plasma membrane, the ILVs are released as "exosomes." The first publication to use the term "exosome" for EVs presented it as a

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Beginning in 2006, several laboratories reported that EVs contain nucleic acids and have the ability to transfer them from cell to cell. Nucleic acids including DNAs and RNAs were even found to be functional in the recipient cell. Whether carrying DNA, RNA, surface molecules, or other factors, the

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through Calixarene, can slow down progression of experimental pancreatic cancer. 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

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Using EVs to profile RNA expression patterns could therefore help diagnose certain diseases before a patient become symptomatic. 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,

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EVs also have senolytic potential. EVs harvested from cardio-sphere-derived cells in young rats have been shown to reverse senescent processes in aged rats. The older rats’ endurance and cardiovascular function improved when they received a transfusion of EVs from younger animals. It is therefore

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The fate of T cells can be determined by the transfer of telomeres via EVs from APCs. T cells that acquire telomeres in such a manner regain stem-like characteristics, avoiding senescence. The creation of long-lived memory T cells via an EV injection of telomeres enhances long-term immunological

442:(e.g., of adult humans) also fulfill the consensus definition of EVs. Especially in the field of platelet research, MP has been the standard nomenclature. Formation of ectosomes may in some cases result from directed processes, and in others from shear forces or adherence of the PM to a surface. 704:

Furthermore, EVs play a role in overall chronic inflammation. The interorgan shuttling of EVs can mean that one disease is likely to promote the advancement of another, as is the case with NAFLD and the development of atherosclerosis. EVs released from steatosis-affected hepatocytes induce the

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EVs facilitate communication between different parts of the CNS, and therefore, EVs found in the blood of neurological patients contain molecules implicated in neurodegenerative diseases. EVs carrying myeloid cargo, for example, have long been recognized as a biomarker of brain inflammation.

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release of inflammatory molecules from endothelial cells co-cultured with them. The co-cultured cells also show increased NF-κB activity. It has thus been demonstrated that EVs released by hepatocytes under NAFLD conditions cause vascular endothelial inflammation and promote atherosclerosis.

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In addition to the very large EVs released during apoptosis, micron-sized EVs may be produced by cancer cells, neurons, and other cells. When produced by cancer cells, these particles are termed "large oncosomes" and may reach 20 microns or more in diameter. Large oncosomes can attain sizes

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in a mouse model and a human fibroblast cell culture model of prostate cancer. Cellular internalization of large oncosomes can reprogram non-neoplastic brain cells to divide and migrate in primary tissue culture, and higher numbers of large oncosomes isolated from blood samples from

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with the plasma membrane. During this time, EVs were described by many names, sometimes in the same manuscript, such as "shedding vesicles," "membrane fragments," "plasma membrane vesicles," "micro-vesicles/microvesicles," "exosomes," (previously used for mobile, transforming

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Cordeiro HG, Azevedo-Martins JM, Faria AV, Rocha-Brito KJ, Milani R, Peppelenbosch M, Fuhler G, de Fátima Â, Ferreira-Halder CV (April 2024). "Calixarene dismantles extracellular vesicle biogenesis and metalloproteinases that support pancreatic cancer hallmarks".

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Multia E, Tear CJ, Palviainen M, Siljander P, Riekkola ML (December 2019). "Fast isolation of highly specific population of platelet-derived extracellular vesicles from blood plasma by affinity monolithic column, immobilized with anti-human CD61 antibody".

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were first observed in rat kidney cell culture, but they are produced by mouse and human cells as well. Damaged mitochondria can be expelled from migrating cells inside of migrasomes, suggesting a functional role for this EV in mitochondrial homeostasis.

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Mack M, Kleinschmidt A, Brühl H, Klier C, Nelson PJ, Cihak J, et al. (July 2000). "Transfer of the chemokine receptor CCR5 between cells by membrane-derived microparticles: a mechanism for cellular human immunodeficiency virus 1 infection".

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Morani M, Mai TD, Krupova Z, Defrenaix P, Multia E, Riekkola ML, Taverna M (September 2020). "Electrokinetic characterization of extracellular vesicles with capillary electrophoresis: A new tool for their identification and quantification".

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is composed of cellular membranes but contains proteins and nucleic acids produced from the viral genome. Some enveloped viruses can infect other cells even without a functional virion, when genomic material is transferred via EVs. Certain

592:, or species of RNA. It has been proposed that purity of an EV preparation can be estimated by examining the ratio of one population-level measurement to another, e.g., the ratio of total protein or total lipid to total particles. 313:

labs forged a deeper understanding of the release of EVs from reticulocytes, while progress was also made on EVs shed from tumor cells. The reticulocyte research, in particular, showed that EVs could be released not only from the

513:. They are hypothesized to be a mechanism for disposal of unwanted cellular material including protein aggregates and damaged organelles. Exophers can remain connected to the cell body by a thin, membranous filament resembling a 254:

Although the extracellular and vesicular properties of EVs had been recognized by numerous groups by the 1970s, the term "extracellular vesicle" was first used in a manuscript title in 1971. This electron microscopy study of the

473:(PS) in the outer bilayer of the cell membrane, apoptotic bodies tend to externalize PS, although other EVs may also do so. Apoptotic bodies may be quite large (microns in diameter) but may also measure in the submicron range. 614:

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: For example, the MISEV2018 guidelines recommend:

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Chen, Tzu-Yi; Gonzalez-Kozlova, Edgar; Soleymani, Taliah; La Salvia, Sabrina; Kyprianou, Natasha; Sahoo, Susmita; Tewari, Ashutosh K.; Cordon-Cardo, Carlos; Stolovitzky, Gustavo; Dogra, Navneet (2022-06-17).

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EVs are believed to play a role in the spreading of different diseases. Studies have shown that tumor cells send EVs to send signal to target resident cells, which can lead to tumor invasion and metastasis.

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Harding C, Heuser J, Stahl P (November 1984). "Endocytosis and intracellular processing of transferrin and colloidal gold-transferrin in rat reticulocytes: demonstration of a pathway for receptor shedding".

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Nunez EA, Wallis J, Gershon MD (October 1974). "Secretory processes in follicular cells of the bat thyroid. 3. The occurrence of extracellular vesicles and colloid droplets during arousal from hibernation".

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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.

4880:"Extracellular Vesicles in Physiology, Pathology, and Therapy of the Immune and Central Nervous System, with Focus on Extracellular Vesicles Derived from Mesenchymal Stem Cells as Therapeutic Tools" 2141:

Ratajczak J, Wysoczynski M, Hayek F, Janowska-Wieczorek A, Ratajczak MZ (September 2006). "Membrane-derived microvesicles: important and underappreciated mediators of cell-to-cell communication".

3111:"Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines" 3291:

Minciacchi VR, Spinelli C, Reis-Sobreiro M, Cavallini L, You S, Zandian M, Li X, Mishra R, Chiarugi P, Adam RM, Posadas EM, Viglietto G, Freeman MR, Cocucci E, Bhowmick NA, Di Vizio D (2017).

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Van Deun J, Mestdagh P, Agostinis P, Akay Ö, Anand S, Anckaert J, et al. (February 2017). "EV-TRACK: transparent reporting and centralizing knowledge in extracellular vesicle research".

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to mice. When genetically modified to express aggregating proteins, neurons were observed to sequester the aggregates into a portion of the cell and release them within a large EV called an

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Chetty VK, Ghanam J, Anchan S, Reinhardt K, Brenzel A, Gelléri M, Cremer C, Grueso-Navarro E, Schneider M, von Neuhoff N, Reinhardt D, Jablonska J, Nazarenko I, Thakur BK (April 2022).

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Valadi H, Ekström K, Bossios A, Sjöstrand M, Lee JJ, Lötvall JO (June 2007). "Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells".

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conditioned medium with distinctions made between "vesicles of the multivesicular body" and "microvesicles." These studies further noted the similarities of EVs and enveloped viruses.

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and others. A clinical trial of dendritic cell-derived EVs was performed in France just before the turn of the century. Cells of the immune system were found capable of transferring

4071:"Minimal experimental requirements for definition of extracellular vesicles and their functions: a position statement from the International Society for Extracellular Vesicles" 3332:

Bertolini I, Terrasi A, Martelli C, Gaudioso G, Di Cristofori A, Storaci AM, Formica M, Braidotti P, Todoerti K, Ferrero S, Caroli M, Ottobrini L, Vaccari T, Vaira V (2019).

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Jiang F, Chen Q, Wang W, Ling Y, Yan Y, Xia P (January 2020). "Hepatocyte-derived extracellular vesicles promote endothelial inflammation and atherogenesis via microRNA-1".

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Ostrowski M, Carmo NB, Krumeich S, Fanget I, Raposo G, Savina A, et al. (January 2010). "Rab27a and Rab27b control different steps of the exosome secretion pathway".

294:) referred back to even earlier publications that furnished similar evidence, although conclusions about EV release had not then been drawn. EVs were also described in 2186:"Alteration of marrow cell gene expression, protein production, and engraftment into lung by lung-derived microvesicles: a novel mechanism for phenotype modulation" 1626:

Pan BT, Johnstone RM (July 1983). "Fate of the transferrin receptor during maturation of sheep reticulocytes in vitro: selective externalization of the receptor".

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Furthermore, nucleic acids corresponding to APP, Aβ42, BACE1, and tau protein biomarkers were found to be associated with different neurodegenerative diseases.

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At least one "negative" or "depleted" marker: a "deep cellular" marker, a marker of a non-EV particle, or a soluble molecule not thought to be enriched in EVs.

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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

865:"The human neurosecretome: extracellular vesicles and particles (EVPs) of the brain for intercellular communication, therapy, and liquid-biopsy applications" 236: 755:

was found in EVs secreted by astrocyte exposed to amyloid beta. An oncogenic mechanism illustrates how extracellular vesicles are produced by proliferative

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Extracellular vesicles and particles (EVPs) are released by cells in different shapes and sizes. Diverse EV subtypes have been proposed, with names such as

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in eukaryotic cells. The latter proteins may be found in large EVs or indeed any EVs, but are expected to be less concentrated in the EV than in the cell.

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synonym for "micro-vesicle." The term has also been used for EVs within specific size ranges, EVs separated using specific methods, or even all EVs.

414: 248: 965:

Moghassemi, Saeid; Dadashzadeh, Arezoo; Sousa, Maria João; Vlieghe, Hanne; Yang, Jie; León-Félix, Cecibel María; Amorim, Christiani A. (June 2024).

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could be transferred from an HIV-susceptible cell to a refractory cell by "microparticles," rendering the recipient cell susceptible to infection.

194: 1456:

De Broe M, Wieme R, Roels F (December 1975). "Letter: Membrane fragments with koinozymic properties released from villous adenoma of the rectum".

2037:"Platelet- and megakaryocyte-derived microparticles transfer CXCR4 receptor to CXCR4-null cells and make them susceptible to infection by X4-HIV" 232: 601:

that have been used successfully for single-EV analysis include optical microscopy and flow cytometry (for large EVs, usually >200 nm),

339:), "inclusion vesicles," and more, or referred to by organ of origin, such as "prostasomes" that were found to enhance sperm motility in semen. 2086:"Tumour-derived microvesicles carry several surface determinants and mRNA of tumour cells and transfer some of these determinants to monocytes" 306: 295: 2389:"Efficient Small Extracellular Vesicles (EV) Isolation Method and Evaluation of EV-Associated DNA Role in Cell-Cell Communication in Cancer" 606:

individual EVs without extensive prior separation from a biological matrix: to give a few examples, electron microscopy and flow cytometry.

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The terms "ectosome," "microvesicle" (MV), and "microparticle" (MP) refer to particles released from the surface of cells. Technically, the

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Separated or concentrated populations of EVs may be characterized by several means. Total concentration of molecules in categories such as

722:(TF). TF is the most potent initiator of the coagulation cascade and is under normal conditions mainly contained to subvascular tissue. 2945:-dendritic cell interaction show modulatory properties and confer resistance to lethal infection as a cell-free based therapy strategy" 406: 57:

or more, although the vast majority of EVs are smaller than 200 nm. EVs can be divided according to size and synthesis route into

4690:"Increased Release of Apolipoprotein E in Extracellular Vesicles Following Amyloid-β Protofibril Exposure of Neuroglial Co-Cultures" 4976:

Urbanelli L, Buratta S, Sagini K, Ferrara G, Lanni M, Emiliani C (2015). "Exosome-based strategies for Diagnosis and Therapy".

1699:"Vesicle formation during reticulocyte maturation. Association of plasma membrane activities with released vesicles (exosomes)" 17: 1413:

Chandler RL, Bird RG, Bland AP (November 1975). "Letter: Particles associated with microvillous border of intestinal mucosa".

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Numerous functions of EVs have been established or postulated. The first evidence for the existence of EVs was enabled by the

805:"Extracellular vesicles carry distinct proteo-transcriptomic signatures that are different from their cancer cell of origin" 3883:"Impact of pre-analytical parameters on the measurement of circulating microparticles: towards standardization of protocol" 622:

At least one cytoplasmic but ideally membrane-associated marker to show that the particle is not merely a membrane fragment

4739:"Acute lymphoblastic leukemia-derived extracellular vesicles affect quiescence of hematopoietic stem and progenitor cells" 4163:"Unravelling the proteomic landscape of extracellular vesicles in prostate cancer by density-based fractionation of urine" 1738:

Dvorak HF, Quay SC, Orenstein NS, Dvorak AM, Hahn P, Bitzer AM, Carvalho AC (May 1981). "Tumor shedding and coagulation".

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Trams EG, Lauter CJ, Salem N, Heine U (July 1981). "Exfoliation of membrane ecto-enzymes in the form of micro-vesicles".

188:. When EVs are taken up by other cells, they may alter the behaviour of the recipient cell, for instance EVs released by 4835:

Agnati LF, Guidolin D, Guescini M, Genedani S, Fuxe K (September 2010). "Understanding wiring and volume transmission".

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Nicolás-Ávila JA, Lechuga-Vieco AV, Esteban-Martínez L, Sánchez-Díaz M, Díaz-García E, Santiago DJ, et al. (2020).

2795:"Proteomic comparison defines novel markers to characterize heterogeneous populations of extracellular vesicle subtypes" 145:

pathway, cargo, cellular source, and function, leading to a historically heterogenous nomenclature including terms like

1049:"Colorectal Cancer Cell-Derived Small Extracellular Vesicles Educate Human Fibroblasts to Stimulate Migratory Capacity" 1008:"Comparison of methods to isolate proteins from extracellular vesicles for mass spectrometry-based proteomic analyses" 3047:"Review of the Isolation, Characterization, Biological Function, and Multifarious Therapeutic Approaches of Exosomes" 2325:

Pegtel DM, Cosmopoulos K, Thorley-Lawson DA, van Eijndhoven MA, Hopmans ES, Lindenberg JL, et al. (April 2010).

374: 199: 5013:"Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers" 4788:"An intercellular transfer of telomeres rescues T cells from senescence and promotes long-term immunological memory" 4639:"Accumulation of amyloid-β by astrocytes result in enlarged endosomes and microvesicle-induced apoptosis of neurons" 2278:"Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers" 5093: 505:

Exophers are a class of large EV, approximately four microns in diameter, observed in model organisms ranging from

377:. A plethora of national and regional EV societies have also been formed. In 2012, the Director's Office of the US 45:

but, unlike a cell, cannot replicate. EVs range in diameter from near the size of the smallest physically possible

602: 342:

The involvement of EVs in immune responses became increasingly clear in the 1990s with findings of the group of

4390:"Rejuvenating effects of young extracellular vesicles in aged rats and in cellular models of human senescence" 3661:"Obstacles and opportunities in the functional analysis of extracellular vesicle RNA - an ISEV position paper" 1579:"Letter: Serum extracellular vesicles profiling is associated with COVID-19 progression and immune responses" 1502:

Benz EW, Moses HL (June 1974). "Small, virus-like particles detected in bovine sera by electron microscopy".

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Dalton AJ (May 1975). "Microvesicles and vesicles of multivesicular bodies versus "virus-like" particles".

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comparable to individual cells, but they do not contain full nuclei. They have been shown to contribute to

3504:"Discovery of the migrasome, an organelle mediating release of cytoplasmic contents during cell migration" 1783:"DNA-induced transformation in Drosophila: locus-specificity and the establishment of transformed stocks" 3932:"Standardization of sample collection, isolation and analysis methods in extracellular vesicle research" 3772:"Automated On-Line Isolation and Fractionation System for Nanosized Biomacromolecules from Human Plasma" 3551:

Jiao H, Jiang D, Hu X, Du W, Ji L, Yang Y, Li X, Sho T, Wang X, Li Y, Wu YT, Wei YH, Hu X, Yu L (2021).

2479:

Hoshino A, Costa-Silva B, Shen TL, Rodrigues G, Hashimoto A, Tesic Mark M, et al. (November 2015).

2184:

Aliotta JM, Sanchez-Guijo FM, Dooner GJ, Johnson KW, Dooner MS, Greer KA, et al. (September 2007).

2084:

Baj-Krzyworzeka M, Szatanek R, Weglarczyk K, Baran J, Urbanowicz B, Brański P, et al. (July 2006).

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Bonucci E (1970). "Fine structure and histochemistry of "calcifying globules" in epiphyseal cartilage".

373:(ISEV), which has led efforts for rigor and standardization in the field including establishment of the 3334:"A GBM-like V-ATPase signature directs cell-cell tumor signaling and reprogramming via large oncosomes" 2536:

Peinado H, Alečković M, Lavotshkin S, Matei I, Costa-Silva B, Moreno-Bueno G, et al. (June 2012).

3979:

Coumans FA, Brisson AR, Buzas EI, Dignat-George F, Drees EE, El-Andaloussi S, et al. (May 2017).

2939:

Gutierrez BC, Ancarola ME, Volpato-Rossi I, Marcilla A, Ramirez MI, Rosenzvit MC, et al. (2022).

2538:"Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET" 1899:

Stegmayr B, Ronquist G (1982). "Promotive effect on human sperm progressive motility by prostasomes".

619:

At least one membrane-associated marker as evidence of the lipid bilayer (e.g., a tetraspanin protein)

4737:

Georgievski A, Michel A, Thomas C, Mlamla Z, Pais de Barros JP, Lemaire-Ewing S, et al. (2022).

211:

Evidence for the existence of EVs and their functions was first gathered by combined applications of

5011:

Skog J, Würdinger T, van Rijn S, Meijer DH, Gainche L, Sena-Esteves M, et al. (December 2008).

2276:

Skog J, Würdinger T, van Rijn S, Meijer DH, Gainche L, Sena-Esteves M, et al. (December 2008).

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an essential role in senescence by negatively regulating the suppressors of p53, for example.

4161:

Dhondt B, Geeurickx E, Tulkens J, Van Deun J, Vergauwen G, Lippens L, et al. (11 March 2020).

3386:

Melentijevic I, Toth ML, Arnold ML, Guasp RJ, Harinath G, Nguyen KC, et al. (February 2017).

2793:

Kowal J, Arras G, Colombo M, Jouve M, Morath JP, Primdal-Bengtson B, et al. (February 2016).

65:

and apoptotic bodies. The composition of EVs varies depending on their parent cells, encompassing

4637:

Söllvander S, Nikitidou E, Brolin R, Söderberg L, Sehlin D, Lannfelt L, Erlandsson A (May 2016).

4388:

Grigorian Shamagian L, Rogers RG, Luther K, Angert D, Echavez A, Liu W, et al. (July 2023).

2035:

Rozmyslowicz T, Majka M, Kijowski J, Murphy SL, Conover DO, Poncz M, et al. (January 2003).

1942:

Raposo G, Nijman HW, Stoorvogel W, Liejendekker R, Harding CV, Melief CJ, Geuze HJ (March 1996).

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Subedi P, Schneider M, Philipp J, Azimzadeh O, Metzger F, Moertl S, et al. (November 2019).

967:"Extracellular vesicles in nanomedicine and regenerative medicine: A review over the last decade" 4446: 3109:

Théry C, Witwer KW, Aikawa E, Alcaraz MJ, Anderson JD, Andriantsitohaina R, et al. (2018).

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cells and can target and compromise a healthy hematopoiesis system during leukemia development.

3881:

Lacroix R, Judicone C, Poncelet P, Robert S, Arnaud L, Sampol J, Dignat-George F (March 2012).

3659:

Mateescu B, Kowal EJ, van Balkom BW, Bartel S, Bhattacharyya SN, Buzás EI, et al. (2017).

2585:

Melo SA, Sugimoto H, O'Connell JT, Kato N, Villanueva A, Vidal A, et al. (November 2014).

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Verderio C, Muzio L, Turola E, Bergami A, Novellino L, Ruffini F, et al. (October 2012).

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Morello M, Minciacchi VR, de Candia P, Yang J, Posadas E, Kim H, et al. (November 2013).

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Bazzan E, Tinè M, Casara A, Biondini D, Semenzato U, Cocconcelli E, et al. (June 2021).

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Leslie M (August 2013). "Cell Biology. NIH effort gambles on mysterious extracellular RNAs".

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Owens, A. Phillip; Mackman, Nigel (2011-05-13). Weber, Christian; Mause, Sebastian (eds.).

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Xu D, Tahara H (March 2013). "The role of exosomes and microRNAs in senescence and aging".

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Multia E, Liangsupree T, Jussila M, Ruiz-Jimenez J, Kemell M, Riekkola ML (October 2020).

8: 4588:"Tumour-Derived Extracellular Vesicles (EVs): A Dangerous "Message in A Bottle" for Bone" 3388:"C. elegans neurons jettison protein aggregates and mitochondria under neurotoxic stress" 543: 319: 216: 212: 161: 4422: 4405: 4389: 4214:"Roles of extracellular vesicles in the aging microenvironment and age-related diseases" 3833: 3722: 3617: 3403: 2858:

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2810: 2651: 2587:"Cancer exosomes perform cell-independent microRNA biogenesis and promote tumorigenesis" 2496: 2342: 2110: 2085: 1857: 1798: 1751: 991: 966: 891: 864: 369:

Rapid growth of the EV research community in the early 2000s led to the creation of the

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Lanna A, Vaz B, D'Ambra C, Valvo S, Vuotto C, Chiurchiù V, et al. (October 2022).

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Kamerkar S, LeBleu VS, Sugimoto H, Yang S, Ruivo CF, Melo SA, et al. (June 2017).

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1075: 1048: 942: 915: 837: 589: 581: 514: 470: 121:. Most cells that have been studied to date are thought to release EVs, including some 5063: 4989: 4848: 4688:

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4069:

Lötvall J, Hill AF, Hochberg F, Buzás EI, Di Vizio D, Gardiner C, et al. (2014).

3442: 1876: 1841: 1817: 1782: 1715: 1698: 1469: 1426: 1216: 1199: 751:. The content of the EVs was also affected by the exposure to amyloid beta and higher 5083: 5042: 4993: 4950: 4911: 4852: 4817: 4768: 4719: 4670: 4619: 4568: 4517: 4466: 4427: 4374: 4362: 4327: 4278: 4243: 4194: 4147: 4135: 4100: 4051: 4043: 4002: 3961: 3904: 3899: 3882: 3867: 3855: 3801: 3756: 3744: 3690: 3641: 3586: 3574: 3533: 3488: 3476: 3425: 3363: 3314: 3273: 3224: 3175: 3171: 3140: 3078: 3027: 2976: 2918: 2883: 2854:"Why the need and how to approach the functional diversity of extracellular vesicles" 2834: 2767: 2718: 2673: 2616: 2567: 2518: 2461: 2420: 2366: 2307: 2250: 2215: 2158: 2115: 2058: 2053: 2036: 2009: 1973: 1916: 1881: 1822: 1763: 1720: 1679: 1643: 1639: 1608: 1559: 1519: 1473: 1430: 1395: 1351: 1313: 1256: 1221: 1180: 1116: 1080: 1047:

Clerici SP, Peppelenbosch M, Fuhler G, Consonni SR, Ferreira-Halder CV (2021-07-15).

1029: 947: 896: 842: 824: 584:. Overall levels of unique molecules can also be measured in the population, such as 451: 402: 189: 146: 58: 4962: 4864: 4494:

Yamamoto S, Azuma E, Muramatsu M, Hamashima T, Ishii Y, Sasahara M (November 2016).

3916: 2779: 2730: 2127: 2021: 1928: 1655: 1485: 1442: 1268: 982: 219:, and functional studies during the mid-20th century. Ultracentrifuged pellets from 5032: 5024: 4985: 4942: 4930: 4901: 4891: 4878:

Koniusz S, Andrzejewska A, Muraca M, Srivastava AK, Janowski M, Lukomska B (2016).

4844: 4807: 4799: 4758: 4750: 4709: 4701: 4660: 4650: 4609: 4599: 4558: 4548: 4507: 4474: 4458: 4417: 4409: 4354: 4317: 4309: 4270: 4233: 4225: 4184: 4174: 4127: 4090: 4082: 4033: 3992: 3951: 3943: 3894: 3845: 3837: 3791: 3783: 3734: 3726: 3680: 3672: 3631: 3621: 3564: 3523: 3515: 3466: 3456: 3415: 3407: 3353: 3345: 3304: 3263: 3255: 3214: 3206: 3167: 3130: 3122: 3068: 3058: 3017: 3007: 2966: 2956: 2910: 2873: 2865: 2824: 2814: 2757: 2708: 2700: 2663: 2655: 2606: 2598: 2557: 2549: 2508: 2500: 2451: 2410: 2400: 2356: 2346: 2297: 2289: 2262: 2242: 2205: 2197: 2170: 2150: 2105: 2097: 2070: 2048: 2001: 1963: 1955: 1908: 1871: 1861: 1812: 1802: 1755: 1710: 1635: 1598: 1590: 1551: 1511: 1465: 1422: 1387: 1363: 1343: 1303: 1295: 1248: 1211: 1170: 1162: 1151:"Biological properties of extracellular vesicles and their physiological functions" 1108: 1070: 1060: 1019: 986: 978: 937: 927: 886: 876: 832: 816: 752: 287: 268: 177: 4462: 4313: 4179: 3997: 3980: 3676: 3309: 3292: 3126: 2636:"Exosomes facilitate therapeutic targeting of oncogenic KRAS in pancreatic cancer" 1112: 4931:"Myeloid microvesicles are a marker and therapeutic target for neuroinflammation" 4038: 4021: 3787: 3293:"MYC Mediates Large Oncosome-Induced Fibroblast Reprogramming in Prostate Cancer" 2914: 639: 534: 315: 157: 3930:

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3349: 2602: 2201: 5078: 4803: 4754: 4413: 4358: 4274: 3606: