Extracellular vesicles (EVs) are lipid bilayer-delimited particles that are naturally released from almost all types of cells but, unlike a cell, cannot replicate. 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.[1][2] 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.[3][4] 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.[5] 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.[6] 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.
^Soleymani T, Chen TY, Gonzalez-Kozlova E, Dogra N (2023). "The human neurosecretome: extracellular vesicles and particles (EVPs) of the brain for intercellular communication, therapy, and liquid-biopsy applications". Frontiers in Molecular Biosciences. 10: 1156821. doi:10.3389/fmolb.2023.1156821. PMC 10229797. PMID 37266331.
^Veziroglu EM, Mias GI (2020-07-17). "Characterizing Extracellular Vesicles and Their Diverse RNA Contents". Frontiers in Genetics. 11: 700. doi:10.3389/fgene.2020.00700. PMC 7379748. PMID 32765582.
^Moghassemi, Saeid; Dadashzadeh, Arezoo; Sousa, Maria João; Vlieghe, Hanne; Yang, Jie; León-Félix, Cecibel María; Amorim, Christiani A. (June 2024). "Extracellular vesicles in nanomedicine and regenerative medicine: A review over the last decade". Bioactive Materials. 36: 126–156. doi:10.1016/j.bioactmat.2024.02.021. PMC 10915394.
^Subedi P, Schneider M, Philipp J, Azimzadeh O, Metzger F, Moertl S, et al. (November 2019). "Comparison of methods to isolate proteins from extracellular vesicles for mass spectrometry-based proteomic analyses". Analytical Biochemistry. 584: 113390. doi:10.1016/j.ab.2019.113390. PMID 31401005.
^Clerici SP, Peppelenbosch M, Fuhler G, Consonni SR, Ferreira-Halder CV (2021-07-15). "Colorectal Cancer Cell-Derived Small Extracellular Vesicles Educate Human Fibroblasts to Stimulate Migratory Capacity". Frontiers in Cell and Developmental Biology. 9: 696373700. doi:10.3389/fcell.2021.696373. PMC 8320664. PMID 34336845.
^ Cordeiro HG, Azevedo-Martins JM, Faria AV, Rocha-Brito KJ, Milani R, Peppelenbosch M, Fuhler G, de Fátima Â, Ferreira-Halder CV (April 2024). "Calix[6]arene dismantles extracellular vesicle biogenesis and metalloproteinases that support pancreatic cancer hallmarks". Cellular Signalling. 119: 111174. doi:10.1016/j.cellsig.2024.111174. PMID 38604340.
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