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      A brief history of nearly EV‐erything – The rise and rise of extracellular vesicles

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          Abstract

          Extracellular vesicles (EVs) are small cargo‐bearing vesicles released by cells into the extracellular space. The field of EVs has grown exponentially over the past two decades; this growth follows the realisation that EVs are not simply a waste disposal system as had originally been suggested by some, but also a complex cell‐to‐cell communication mechanism. Indeed, EVs have been shown to transfer functional cargo between cells and can influence several biological processes. These small biological particles are also deregulated in disease. As we approach the 75th anniversary of the first experiments in which EVs were unknowingly isolated, it seems right to take stock and look back on how the field started, and has since exploded into its current state. Here we review the early experiments, summarise key findings that have propelled the field, describe the growth of an organised EV community, discuss the current state of the field, and identify key challenges that need to be addressed.

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          Most cited references120

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          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

          ABSTRACT The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.
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            Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells.

            Exosomes are vesicles of endocytic origin released by many cells. These vesicles can mediate communication between cells, facilitating processes such as antigen presentation. Here, we show that exosomes from a mouse and a human mast cell line (MC/9 and HMC-1, respectively), as well as primary bone marrow-derived mouse mast cells, contain RNA. Microarray assessments revealed the presence of mRNA from approximately 1300 genes, many of which are not present in the cytoplasm of the donor cell. In vitro translation proved that the exosome mRNAs were functional. Quality control RNA analysis of total RNA derived from exosomes also revealed presence of small RNAs, including microRNAs. The RNA from mast cell exosomes is transferable to other mouse and human mast cells. After transfer of mouse exosomal RNA to human mast cells, new mouse proteins were found in the recipient cells, indicating that transferred exosomal mRNA can be translated after entering another cell. In summary, we show that exosomes contain both mRNA and microRNA, which can be delivered to another cell, and can be functional in this new location. We propose that this RNA is called "exosomal shuttle RNA" (esRNA).
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              Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication

              The ability of exosomes to transfer cargo from donor to acceptor cells, thereby triggering phenotypic changes in the latter, has generated substantial interest in the scientific community. However, the extent to which exosomes differ from other extracellular vesicles in terms of their biogenesis and functions remains ill-defined. Here, we discuss the current knowledge on the specificities of exosomes and other types of extracellular vesicles, and their roles as important agents of cell-to-cell communication.
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                Author and article information

                Contributors
                dcarter@brookes.ac.uk
                Journal
                J Extracell Vesicles
                J Extracell Vesicles
                10.1002/(ISSN)2001-3078
                JEV2
                Journal of Extracellular Vesicles
                John Wiley and Sons Inc. (Hoboken )
                2001-3078
                17 December 2021
                December 2021
                : 10
                : 14 ( doiID: 10.1002/jev2.v10.14 )
                : e12144
                Affiliations
                [ 1 ] Acute Stroke Programme, Radcliffe Department of Medicine University of Oxford, John Radcliffe Hospital, Headley Way, Headington Oxford UK
                [ 2 ] Department of Genetics, Cell‐ and Immunobiology Semmelweis University Budapest Hungary
                [ 3 ] ELKH‐SE Immune‐Proteogenomics Extracellular Vesicle Research Group Budapest Hungary
                [ 4 ] HCEMM‐SU Extracellular Vesicles Research Group Budapest Hungary
                [ 5 ] Department of Surgery Pathology & Laboratory Medicine Cedars‐Sinai Medical Center Los Angeles California USA
                [ 6 ] Department of Life Sciences Pohang University of Science and Technology Pohang Republic of Korea
                [ 7 ] Institute of Inflammation and Ageing College of Medical and Dental Sciences University of Birmingham Edgbaston Birmingham UK
                [ 8 ] Department of Biochemistry and Genetics La Trobe Institute for Molecular Science La Trobe University Bundoora Victoria Australia
                [ 9 ] Krefting Research Centre Institute of Medicine Sahlgrenska Academy at University of Gothenburg Gothenburg Sweden
                [ 10 ] Institut Curie Paris Sciences et Lettres Research University Centre National de la Recherche Scientifique UMR144, Structure and Membrane Compartments Paris France
                [ 11 ] Department of Cell Biology Washington University School of Medicine St Louis Missouri USA
                [ 12 ] INSERM U932 Institut Curie Paris Sciences et Lettres Research University Paris France
                [ 13 ] Molecular and Comparative Pathobiology and Neurology, and The Richman Family Precision Medicine Center of Excellence in Alzheimer’s Disease The Johns Hopkins University School of Medicine Baltimore Maryland USA
                [ 14 ] Department of Biological and Medical Sciences Faculty of Health and Life Sciences Oxford Brookes University Oxford UK
                [ 15 ] Evox Therapeutics Limited Oxford Science Park Oxford OX4 4HG UK
                Author notes
                [*] [* ] Correspondence

                David RF Carter, Evox Therapeutics Limited, Oxford Science Park, Oxford, OX4 4HG, UK.

                Email: dcarter@brookes.ac.uk

                Author information
                https://orcid.org/0000-0002-5623-5568
                Article
                JEV212144
                10.1002/jev2.12144
                8681215
                34919343
                c77179f8-18cb-4eab-8ef2-efc8302961b4
                © 2021 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 06 August 2021
                : 19 May 2021
                : 28 August 2021
                Page count
                Figures: 2, Tables: 0, Pages: 12, Words: 10306
                Funding
                Funded by: BBSRC , doi 10.13039/501100000268;
                Award ID: BB/P006205/1
                Funded by: Cancer Research UK , doi 10.13039/501100000289;
                Award ID: A28052
                Funded by: Alzheimer's Research UK
                Award ID: ARUK‐RF2019B‐004
                Funded by: NIH/NCI
                Award ID: DDV: R01CA234557
                Award ID: R01CA218526
                Award ID: KWW: AI144997
                Award ID: DA047807
                Award ID: MH118164
                Award ID: CA241694
                Funded by: Michael J. Fox Foundation , doi 10.13039/100000864;
                Funded by: Scar Free Foundation and the National Institute for Health Research (NIHR) Surgical Reconstruction and Microbiology Research Centre (SRMRC)
                Categories
                Review Article
                Review Articles
                Custom metadata
                2.0
                December 2021
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.7.0 mode:remove_FC converted:17.12.2021

                ectosome,exosome,extracellular vesicle,microparticle,microvesicle

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