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.

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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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Membrane-associated Hsp72 from tumor-derived exosomes mediates STAT3-dependent immunosuppressive function of mouse and human myeloid-derived suppressor cells.

Fanny Chalmin, Sylvain Ladoire, Grégoire Mignot … (2010)

Myeloid-derived suppressor cells (MDSCs) have been identified in humans and mice as a population of immature myeloid cells with the ability to suppress T cell activation. They accumulate in tumor-bearing mice and humans and have been shown to contribute to cancer development. Here, we have isolated tumor-derived exosomes (TDEs) from mouse cell lines and shown that an interaction between TDE-associated Hsp72 and MDSCs determines the suppressive activity of the MDSCs via activation of Stat3. In addition, tumor-derived soluble factors triggered MDSC expansion via activation of Erk. TDE-associated Hsp72 triggered Stat3 activation in MDSCs in a TLR2/MyD88-dependent manner through autocrine production of IL-6. Importantly, decreasing exosome production using dimethyl amiloride enhanced the in vivo antitumor efficacy of the chemotherapeutic drug cyclophosphamide in 3 different mouse tumor models. We also demonstrated that this mechanism is relevant in cancer patients, as TDEs from a human tumor cell line activated human MDSCs and triggered their suppressive function in an Hsp72/TLR2-dependent manner. Further, MDSCs from cancer patients treated with amiloride, a drug used to treat high blood pressure that also inhibits exosome formation, exhibited reduced suppressor functions. Collectively, our findings show in both mice and humans that Hsp72 expressed at the surface of TDEs restrains tumor immune surveillance by promoting MDSC suppressive functions.

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Vesiclepedia: A Compendium for Extracellular Vesicles with Continuous Community Annotation

Hina Kalra, Richard J. Simpson, Kai-Hong Ji … (2012)

Introduction A growing body of research has implicated extracellular vesicles (EVs), membraneous sacs released by a variety of cells, in diverse physiological and patho-physiological conditions [1]–[9]. They can be detected in body fluids including blood plasma, urine, saliva, amniotic fluid, breast milk, and pleural ascites [10]–[13], and contain proteins, lipids, and RNA representative of the host cell [14]–[18]. Though a definitive categorization is yet to be achieved [19], EVs can be broadly classified into three main classes, based on the mode of biogenesis: (i) ectosomes (also referred to as shedding microvesicles), (ii) exosomes, and (iii) apoptotic bodies (ABs) (see Box 1). Box 1. Categories of EVs Based on the Mode of Biogenesis Ectosomes or shedding microvesicles: Ectosomes are large EVs ranging between 50–1,000 nm in diameter [1]. They are shed from cells by outward protrusion (or budding) of a plasma membrane (PM) followed by fission of their membrane stalk [3],[5]. Ectosomes are released by a variety of cells including tumour cells, polymorphonuclear leucocytes, and aging erythrocytes [5]. The expression of phosphatidylserine (PS) on the membrane surface has been shown to be one of the characteristic features of ectosomes [1],[5]. Exosomes: Exosomes are small membranous vesicles of endocytic origin ranging from 40–100 nm in diameter [1],[42]. The density of exosomes varies from 1.10–1.21 g/ml and the commonly found markers of exosomes are Alix, TSG101, tetraspanins, and heat shock proteins [10]. The biogenesis of exosomes begins with the internalisation of molecules via endocytosis [42]. Once internalised, endocytosed molecules are either recycled to the PM or trafficked to multivesicular bodies (MVBs) [3]. The “exocytic” fate of MVBs results in their exocytic fusion with the PM, resulting in the release of intraluminal vesicles into the extracellular microenvironment as exosomes [43]. Apoptotic bodies: ABs are released from fragmented apoptotic cells and are 50–5,000 nm in diameter [1]. ABs are formed about during the process of programmed cell death or apoptosis, and represent the fragments of dying cells [3]. Similar to ectosomes, the expression of PS on the membrane surface has been shown to be a key characteristic of ABs [1],[5]. Recent studies have highlighted the role of EVs in intercellular communication [20]–[22], vaccine and drug delivery [23]–[25], and suggested a potential role in gene vector therapy [26] and as disease biomarkers [27]. More than three decades of research has advanced our basic understanding of these extracellular organelles and has generated large amounts of multidimensional data [14],[17]. Whilst most of the data are presented in the context of the biological findings/technical development and are mentioned in the inline text of the published article, a vast majority are often placed as supplementary information or not provided [28],[29]. Importantly, none of the molecular data in published articles is easily searchable [28]. With the immense interest in EVs and advances in high-throughput techniques, the data explosion will only increase. An online compendium of heterogeneous data will help the biomedical community to exploit the publicly available datasets and accelerate biological discovery [30]. ExoCarta and Need for an EV Database Existing databases are not comprehensive. For example, ExoCarta (http://www.exocarta.org), a database for molecular data (proteins, RNA, and lipids) identified in exosomes, catalogs only exosomal studies (as reported by the authors) [31]. Described initially in 2009 [32], the database has been visited by more than 16,000 unique users [33]. However, only exosomal studies (as reported by the authors) are catalogued in ExoCarta. With the confusion in terminologies and inefficiency of the purification protocols to clearly segregate each class of EVs [1],[19], it is critical to build a repository with data from all classes of EVs to understand more about the molecular repertoire of the various classes of EVs and their biological functions. This was the rationale for starting the Vesiclepedia online compendium for EVs. Vesiclepedia Vesiclepedia (http://www.microvesicles.org) is a manually curated compendium that contains molecular data identified in all classes of EVs, including AB, exosomes, large dense core vesicles, microparticles, and shedding microvesicles. The main criterion for manual curation was the presence of these vesicles in the extracellular microenvironment (EVs) as approved by the investigators who undertook the research. At this juncture, the EVs are named as per the curated article or submitting author, as the nomenclature is yet to be standardized [19]. Vesiclepedia was built using ZOPE, an open source content management system. Python a portable, interpreted, object oriented programming language was used in the three-tier system to connect the web interface with a MySQL database. Users can query or browse through proteins, lipids, and RNA molecules identified in EVs. Selecting a gene of interest directs the user to a gene/molecule page with information on the gene, its external references to other primary databases, experiment description of the study that identified the molecule, gene ontology based annotations, protein-protein interactions, and a graphical display of such network with relevance to molecules identified in EVs. Gene ontology annotations of molecular functions, biological process, and subcellular localization were retrieved from Entrez Gene [34] and mapped onto the proteins/mRNA identified in EVs. Under the experiment description, the sample source including the tissue name or cell line name, EV isolation procedures, and floatation gradient density as reported in the study are provided to the users. EV proteins are mapped onto their protein physical interactors along with the protein interaction identification method and PubMed identifier. Protein-protein interaction data was obtained from HPRD [35],[36], BioGRID [37], and Human Proteinpedia [38]. Database Issues and Community Annotation Though biological databases are indispensable resources for effective scientific research, it has to be noted that more than 20% of the database links are non-existent after their initial publication [39]–[41]. More than 50% of the databases are never updated reducing their usability [39], primarily due to the lack of continuous funding to maintain and update these resources. At this juncture, funding for databases is largely non-existent in many parts of the world. To overcome funding-related limitations and to keep the database updated, it is essential to involve the scientific community in annotating the data. Community annotation will significantly ease the burden of the curators who maintain and update the databases. Whilst community annotation is the permanent solution to keep the database updated, it seldom happens without a clear and transparent mechanism. In addition, the system has to ensure continuous deposition of data and “not just once” uploads. It has to be noted that data annotation can be regulated at two levels: (i) principal investigators voluntarily contributing data and (ii) peer-reviewed journals mandating data deposition before publication. Currently available community annotation tools don't have a continuous data deposition arrangement with an investigator. Additionally, only few journals mandate the deposition of data to public repositories before acceptance of a manuscript. To this end, we have initiated a community annotation project through Vesiclepedia that involves members of the EV research community (53 laboratories from 20 countries: Table 1). 10.1371/journal.pbio.1001450.t001 Table 1 Vesiclepedia statistics. Statistics n EV studies 341 Protein entries 35,264 mRNA entries 18,718 miRNA entries 1,772 Lipid molecules 342 Participating laboratories 53 Countries 20 Community annotation via Vesiclepedia happens through the founding members who agree to the conditions listed in Box 2. All of the members are listed in the credits page (http://www.microvesicles.org/credits). Box 2. Conditions to Become a Member of Vesiclepedia Community Annotation 1, Agree to submit datasets pertaining to EVs to Vesiclepedia before or after publication on a continuous basis 2, When reviewing articles, mandate/request investigators to submit datasets on EVs to Vesiclepedia On the basis of the agreement of community participation, members will submit their data automatically to Vesiclepedia before or after publication (Figure 1). Non-members submitting their research findings for peer-review through international journals might find the Vesiclepedia members as referees who will request/mandate the authors to submit the data to Vesiclepedia. By instituting this mechanism the datasets will be continuously deposited to Vesiclepedia. However, a non-member can also be appointed as a referee in which case the data might not be submitted to Vesiclepedia. The Vesiclepedia-data capture team will work along with the researchers to make the data submission as easy as possible. Detailed information on the format of data required for submission is provided in the Vesiclepedia webpage (http://www.microvesicles.org/data_submission). Currently, Vesiclepedia comprises 35,264 protein, 18,718 mRNA, 1,772 miRNA, and 342 lipid entries (Table 1). All of these data were obtained from 341 independent studies that were published over the past several years. 10.1371/journal.pbio.1001450.g001 Figure 1 A schematic of Vesiclepedia community annotation. Based on the agreement of community participation, members will submit their data automatically to Vesiclepedia before and after publication. Non-members submitting their research findings for peer-review through international journals might find some of the Vesiclepedia members as referees who will request/mandate the authors to submit the data to Vesiclepedia. Alternatively, a non-member can also be appointed as a referee in which case the data might not be submitted to Vesiclepedia. A non-member can also submit data directly to Vesiclepedia. Conclusions and Future Directions ExoCarta will be active even after the release of Vesiclepedia and will become a primary resource for high-quality exosomal datasets. Data deposited to ExoCarta can also be accessed through Vesiclepedia; however, only high quality exosomal datasets deposited to Vesiclepedia can be accessed through ExoCarta. With the launch of Vesiclepedia, we expect to have an organised data deposition mechanism. We expect active participation from the EV research community, along with the addition of new members and numerous heterogeneous datasets. All datasets submitted by EV researchers will be listed in the credits page along with the investigator details.

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Isolation of exosomes from whole blood by integrating acoustics and microfluidics

Mengxi Wu, Yingshi Ouyang, Zeyu Wang … (2017)

We have developed a unique, integrated, on-chip technology that is capable of isolating exosomes or other types of extracellular vesicles, directly from undiluted whole-blood samples in an automated fashion. Automated exosome isolation enables biohazard containment, short processing time, reproducible results with little human intervention, and convenient integration with downstream exosome analysis units. Our method of integrating acoustics and microfluidics leads to the isolation of exosomes with high purity and yield. With its label-free, contact-free, and biocompatible nature, it offers the potential to preserve the structures, characteristics, and functions of isolated exosomes. This automated, point-of-care device can further help in advancing exosome-related biomedical research with potential applications in health monitoring, disease diagnostics, and therapeutics. Exosomes are nanoscale extracellular vesicles that play an important role in many biological processes, including intercellular communications, antigen presentation, and the transport of proteins, RNA, and other molecules. Recently there has been significant interest in exosome-related fundamental research, seeking new exosome-based biomarkers for health monitoring and disease diagnoses. Here, we report a separation method based on acoustofluidics (i.e., the integration of acoustics and microfluidics) to isolate exosomes directly from whole blood in a label-free and contact-free manner. This acoustofluidic platform consists of two modules: a microscale cell-removal module that first removes larger blood components, followed by extracellular vesicle subgroup separation in the exosome-isolation module. In the cell-removal module, we demonstrate the isolation of 110-nm particles from a mixture of micro- and nanosized particles with a yield greater than 99%. In the exosome-isolation module, we isolate exosomes from an extracellular vesicle mixture with a purity of 98.4%. Integrating the two acoustofluidic modules onto a single chip, we isolated exosomes from whole blood with a blood cell removal rate of over 99.999%. With its ability to perform rapid, biocompatible, label-free, contact-free, and continuous-flow exosome isolation, the integrated acoustofluidic device offers a unique approach to investigate the role of exosomes in the onset and progression of human diseases with potential applications in health monitoring, medical diagnosis, targeted drug delivery, and personalized medicine.

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Author and article information

Journal

Journal ID (iso-abbrev): J Extracell Vesicles

Title: Journal of extracellular vesicles

Publisher: Informa UK Limited

ISSN: 2001-3078

ISSN (Print): 2001-3078

Publication date (Electronic): 2018

Volume: 7

Issue: 1

Affiliations

[1 ] Institut Curie, INSERM U932, PSL Research University, Paris, France.

[2 ] The Johns Hopkins University School of Medicine, Department of Molecular and Comparative Pathobiology, Baltimore, MD, USA.

[3 ] The Johns Hopkins University School of Medicine, Department of Neurology, Baltimore, MD, USA.

[4 ] Brigham and Women's Hospital, Center for Interdisciplinary Cardiovascular Sciences, Boston, MA, USA.

[5 ] Harvard Medical School, Cardiovascular Medicine, Boston, MA, USA.

[6 ] Interuniversity Research Institute for Molecular Recognition and Technological Development (IDM), University of Valencia, Polytechnic University of Valencia, Valencia, Spain.

[7 ] University of California, Davis, Department of Otolaryngology, Davis, CA, USA.

[8 ] INSERM U1063, Université d'Angers, CHU d'Angers, Angers, France.

[9 ] German Centre for Neurodegenerative Diseases (DZNE), Bonn, Germany.

[10 ] University Hospital Bonn (UKB), Bonn, Germany.

[11 ] Université de Lille, INSERM, U-1192, Laboratoire Protéomique, Réponse Inflammatoire et Spectrométrie de Masse - PRISM, Lille, France.

[12 ] University of Lyon, INRA, EPHE, UMR754 Viral Infections and Comparative Pathology, Lyon, France.

[13 ] La Trobe University, La Trobe Institute for Molecular Science, Department of Biochemistry and Genetics, Bundoora, Australia.

[14 ] Atlantic Cancer Research Institute, Moncton, Canada.

[15 ] Mount Allison University, Department of Chemistry and Biochemistry, Sackville, Canada.

[16 ] Université Bretagne Loire, Oniris, INRA, IECM, Nantes, France.

[17 ] University of Cologne, Department of Internal Medicine I, Cologne, Germany.

[18 ] Royan Institute for Stem Cell Biology and Technology, ACECR, Cell Science Research Center, Department of Stem Cells and Developmental Biology, Tehran, Iran.

[19 ] University of Science and Culture, ACECR, Department of Developmental Biology, Tehran, Iran.

[20 ] Massachusetts General Hospital, Department of Neurosurgery, Boston, MA, USA.

[21 ] University of Malta, Department of Pathology, Msida, Malta.

[22 ] University of South Alabama, Department of Pharmacology, Center for Lung Biology, Mobile, AL, USA.

[23 ] University of Technology Sydney, Discipline of Pharmacy, Graduate School of Health, Sydney, Australia.

[24 ] University of Rochester, Rochester, NY, USA.

[25 ] National Institute of Chemistry, Department of Molecular Biology and Nanobiotechnology, Ljubljana, Slovenia.

[26 ] Université Laval, Centre de Recherche du CHU de Québec, Department of Infectious Diseases and Immunity, Quebec City, Canada.

[27 ] Ospedale Santo Spirito, Pescara, Italy.

[28 ] CSGI - Research Center for Colloids and Nanoscience, Florence, Italy.

[29 ] INSTM - National Interuniversity Consortium of Materials Science and Technology, Florence, Italy.

[30 ] University of Brescia, Department of Molecular and Translational Medicine, Brescia, Italy.

[31 ] University of Birmingham, Institute of Microbiology and Infection, Birmingham, UK.

[32 ] University of Auckland, Auckland, New Zealand.

[33 ] Jagiellonian University, Faculty of Biochemistry, Biophysics and Biotechnology, Department of Cell Biology, Kraków, Poland.

[34 ] FEMTO-ST Institute, UBFC, CNRS, ENSMM, UTBM, Besançon, France.

[35 ] Institute of Biomedicine and Molecular Immunology (IBIM), National Research Council (CNR) of Italy, Palermo, Italy.

[36 ] Germans Trias i Pujol Research Institute (IGTP), Can Ruti Campus, REMAR-IVECAT Group, Badalona, Spain.

[37 ] Germans Trias i Pujol University Hospital, Nephrology Service, Badalona, Spain.

[38 ] Universitat Autònoma de Barcelona, Department of Cell Biology, Physiology & Immunology, Barcelona, Spain.

[39 ] INSERM UMR-S 970, Paris Cardiovascular Research Center, Paris, France.

[40 ] Université Paris Descartes, Sorbonne Paris Cité, Paris, France.

[41 ] Massachusetts General Hospital and Neuroscience Program, Harvard Medical School, Department of Neurology and Radiology, Boston, MA, USA.

[42 ] Icahn School of Medicine at Mount Sinai, New York City, NY, USA.

[43 ] National Institutes of Health, National Institute on Deafness and Other Communication Disorders, Bethesda, MD, USA.

[44 ] Harvard University, School of Engineering and Applied Sciences, Cambridge, MA, USA.

[45 ] Massachusetts General Hospital, Harvard Medical School, Department of Neurology, Boston, MA, USA.

[46 ] Université de Nantes, INSERM UMR 1238, Bone Sarcoma and Remodeling of Calcified Tissues, PhyOS, Nantes, France.

[47 ] Nationwide Children's Hospital, Columbus, OH, USA.

[48 ] The Ohio State University, Columbus, OH, USA.

[49 ] UMR-CBMN, CNRS-Université de Bordeaux, Bordeaux, France.

[50 ] Haaglanden Medical Center, Department of Neurosurgery, The Hague, The Netherlands.

[51 ] Leiden University Medical Center, Department of Neurosurgery, Leiden, The Netherlands.

[52 ] Massachusetts General Hospital, Department of Neurology, Boston, MA, USA.

[53 ] Memorial Sloan Kettering Cancer Center, Department of Medicine, New York City, NY, USA.

[54 ] Weill Cornell Medicine, Department of Medicine, New York City, NY, USA.

[55 ] Lund University, Department of Cardiology, Lund, Sweden.

[56 ] University of Nebraska Medical Center, Department of Pharmacology and Experimental Neuroscience, Omaha, NE, USA.

[57 ] University of Edinburgh, Institute of Immunology & Infection Research, Edinburgh, UK.

[58 ] Kidney Research Centre, Ottawa, Canada.

[59 ] Ottawa Hospital Research Institute, Ottawa, Canada.

[60 ] University of Ottawa, Ottawa, Canada.

[61 ] Mayo Clinic, Department of Transplantation, Jacksonville, FL, USA.

[62 ] Technical University of Munich, TUM School of Life Sciences Weihenstephan, Division of Animal Physiology and Immunology, Freising, Germany.

[63 ] University of Torino, Department of Molecular Biotechnology and Health Sciences, Torino, Italy.

[64 ] MTA-SE Immuno-Proteogenomics Research Groups, Budapest, Hungary.

[65 ] Semmelweis University, Department of Genetics, Cell- and Immunobiology, Budapest, Hungary.

[66 ] University of Michigan, Department of Medicine, Ann Arbor, MI, USA.

[67 ] University of Torino, Department of Medical Sciences, Torino, Italy.

[68 ] Oxford Brookes University, Department of Biological and Medical Sciences, Oxford, UK.

[69 ] University of Auckland, Department of Obstetrics and Gynaecology, Auckland, New Zealand.

[70 ] National Taiwan University Hospital, Department of Internal Medicine, Taipei, Taiwan.

[71 ] National Tsing Hua University, Department of Power Mechanical Engineering, Hsinchu, Taiwan.

[72 ] National Tsing Hua University, Institute of Nanoengineering and Microsystems, Hsinchu, Taiwan.

[73 ] Leibniz Institute for Farm Animal Biology (FBN), Institute of Reproductive Biology, Dummerstorf, Germany.

[74 ] Cedars-Sinai Medical Center, Los Angeles, CA, USA.

[75 ] Cardiff University, School of Medicine, Cardiff, UK.

[76 ] UNICAMP, Institute of Biology, Campinas, Brazil.

[77 ] The Ohio State University, College of Pharmacy, Division of Pharmaceutics and Pharmaceutical Chemistry, Columbus, OH, USA.

[78 ] The Ohio State University, Comprehensive Cancer Center, Columbus, OH, USA.

[79 ] Vanderbilt University Medical Center, Epithelial Biology Center, Department of Medicine, Nashville, TN, USA.

[80 ] University of Porto, Faculty of Pharmacy (FFUP), IBMC/I3S, Porto, Portugal.

[81 ] University of Oxford, Radcliffe Department of Medicine, Acute Stroke Programme - Investigative Medicine, Oxford, UK.

[82 ] Academic Medical Centre of the University of Amsterdam, Department of Clinical Chemistry and Vesicle Observation Centre, Amsterdam, The Netherlands.

[83 ] The University of Nottingham, School of Medicine, Children's Brain Tumour Research Centre, Nottingham, UK.

[84 ] University of Gothenburg, Institute of Medicine at Sahlgrenska Academy, Krefting Research Centre, Gothenburg, Sweden.

[85 ] University of São Paulo, Ribeirão Preto Medical School, Ribeirão Preto, Brazil.

[86 ] University of Notre Dame, Department of Biological Sciences, Notre Dame, IN, USA.

[87 ] Massachusetts General Hospital, Boston, MA, USA.

[88 ] IRCCS MultiMedica, Milan, Italy.

[89 ] The Sociedade Beneficente Israelita Brasileira Albert Einstein, São Paulo, Brazil.

[90 ] Cancer Research Institute Ghent, Ghent, Belgium.

[91 ] Ghent University, Department of Radiation Oncology and Experimental Cancer Research, Laboratory of Experimental Cancer Research, Ghent, Belgium.

[92 ] Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.

[93 ] Institut d'Investigació Germans Trias i Pujol (IGTP), PVREX group, Badalona, Spain.

[94 ] ISGlobal, Hospital Clínic - Universitat de Barcelona, PVREX Group, Barcelona, Spain.

[95 ] Université Catholique de Louvain, Institut de Recherche Expérimentale et Clinique (IREC), Laboratory of Pediatric Hepatology and Cell Therapy, Brussels, Belgium.

[96 ] Universiteit Hasselt, Diepenbeek, Belgium.

[97 ] Vlaamse Instelling voor Technologisch Onderzoek (VITO), Mol, Belgium.

[98 ] Aston University, School of Life & Health Sciences, Birmingham, UK.

[99 ] Ghent University Hospital, Department of Urology, Ghent, Belgium.

[100 ] ETH Zurich, Institute of Pharmaceutical Sciences, Zurich, Switzerland.

[101 ] University of L'Aquila, Department of Life, Health and Environmental Sciences, L'Aquila, Italy.

[102 ] Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales, Departamento de Química Biológica, Buenos Aires, Argentina.

[103 ] TPM of Mirandola, Mirandola, Italy.

[104 ] University of Modena and Reggio Emilia, Division of Oncology, Modena, Italy.

[105 ] University of Campinas, Piracicaba Dental School, Department of Oral Diagnosis, Piracicaba, Brazil.

[106 ] University of Oulu, Faculty of Medicine, Cancer and Translational Medicine Research Unit, Oulu, Finland.

[107 ] Utrecht University, Faculty of Veterinary Medicine, Department of Biochemistry and Cell Biology, Utrecht, The Netherlands.

[108 ] Exogenus Therapeutics, Cantanhede, Portugal.

[109 ] McGill University, Division of Experimental Medicine, Montreal, Canada.

[110 ] McGill University, The Research Institute of the McGill University Health Centre, Child Health and Human Development Program, Montreal, Canada.

[111 ] James Cook University, Australian Institute of Tropical Health and Medicine, Centre for Biodiscovery and Molecular Development of Therapeutics, Cairns, Australia.

[112 ] University of Gothenburg, Institute of Clinical Sciences at Sahlgrenska Academy, Department of Biomaterials, Gothenburg, Sweden.

[113 ] Evox Therapeutics Limited, Oxford, UK.

[114 ] Karolinska Institute, Stockholm, Sweden.

[115 ] University of Virginia Health System, Department of Medicine, Division of Nephrology, Charlottesville, VA, USA.

[116 ] CIC bioGUNE, CIBERehd, Exosomes Laboratory & Metabolomics Platform, Derio, Spain.

[117 ] IKERBASQUE Research Science Foundation, Bilbao, Spain.

[118 ] University of São Paulo, Ribeirão Preto Medical School, Department of Pathology and Forensic Medicine, Ribeirão Preto, Brazil.

[119 ] Toronto General Hospital Research Institute, University Health Network, Toronto, Canada.

[120 ] University of Toronto, Department of Laboratory Medicine and Pathobiology, Toronto, Canada.

[121 ] University of Colorado, School of Medicine, Department of Ophthalmology, Cell Sight-Ocular Stem Cell and Regeneration Program, Aurora, CO, USA.

[122 ] German Cancer Research Center (DKFZ), Clinical Cooperation Unit Applied Tumor Biology, Heidelberg, Germany.

[123 ] University Hospital Heidelberg, Institute of Pathology, Applied Tumor Biology, Heidelberg, Germany.

[124 ] Helmholtz-Centre for Infection Research, Braunschweig, Germany.

[125 ] Helmholtz-Institute for Pharmaceutical Research Saarland, Saarbrücken, Germany.

[126 ] Saarland University, Saarbrücken, Germany.

[127 ] Karolinska Institute, Department of Medicine Solna, Division for Immunology and Allergy, Stockholm, Sweden.

[128 ] Universitat Autònoma de Barcelona, Hospital Universitari and Health Sciences Research Institute Germans Trias i Pujol, Department of Pathology, Barcelona, Spain.

[129 ] University College London, London, UK.

[130 ] Helmholtz Center Munich German Research Center for Environmental Health, Research Unit Gene Vectors, Munich, Germany.

[131 ] INSERM U1110, Strasbourg, France.

[132 ] Université de Strasbourg, Strasbourg, France.

[133 ] POSTECH (Pohang University of Science and Technology), Department of Life Sciences, Pohang, South Korea.

[134 ] University Hospital Essen, University Duisburg-Essen, Institute for Transfusion Medicine, Essen, Germany.

[135 ] Paracelsus Medical University, GMP Unit, Salzburg, Austria.

[136 ] University of Oxford, Department of Physiology, Anatomy and Genetics, Oxford, UK.

[137 ] Karolinska Institute, Clinical Research Center, Department of Laboratory Medicine, Stockholm, Sweden.

[138 ] BC Cancer, Canada's Michael Smith Genome Sciences Centre, Vancouver, Canada.

[139 ] Simon Fraser University, Department of Molecular Biology and Biochemistry, Burnaby, Canada.

[140 ] University Medical Center Göttingen, Developmental Biochemistry, Göttingen, Germany.

[141 ] University Medical Center Göttingen, Hematology and Oncology, Göttingen, Germany.

[142 ] IRCCS Fondazione Don Carlo Gnocchi, Laboratory of Nanomedicine and Clinical Biophotonics (LABION), Milan, Italy.

[143 ] Loyola University Chicago, Department of Urology, Maywood, IL, USA.

[144 ] Aalborg University Hospital, Department of Clinical Biochemistry, Aalborg, Denmark.

[145 ] Aalborg University, Clinical Institute, Aalborg, Denmark.

[146 ] University of Massachusetts Medical School, RNA Therapeutics Institute, Worcester, MA, USA.

[147 ] University of Birmingham, Birmingham, UK.

[148 ] Scintillon Institute, La Jolla, CA, USA.

[149 ] University of California, San Diego, Department of Neurosurgery, La Jolla, CA, USA.

[150 ] Aberystwyth University, Institute of Biological, Environmental and Rural Sciences (IBERS), Aberystwyth, United Kingdom.

[151 ] Imperial College London, London, UK.

[152 ] MRC The Gambia, Fajara, The Gambia.

[153 ] University Clinic Eppendorf, Hamburg, Germany.

[154 ] Hasselt University, Biomedical Research Institute (BIOMED), Department of Medicine and Life Sciences, Hasselt, Belgium.

[155 ] Nanfang Hospital, Southern Medical University, Department of Clinical Laboratory Medicine, Guangzhou, China.

[156 ] Fondazione IRCCS Istituto Nazionale dei Tumori, Unit of Immunotherapy of Human Tumors, Milan, Italy.

[157 ] The University of Sheffield, Sheffield, UK.

[158 ] Cedars-Sinai Medical Center, Smidt Heart Institute, Los Angeles, CA, USA.

[159 ] Boston University School of Medicine, Boston, MA, USA.

[160 ] University of Hertfordshire, School of Life and Medical Sciences, Biosciences Research Group, Hatfield, UK.

[161 ] Istanbul University Oncology Institute, Basic Oncology Department, Istanbul, Turkey.

[162 ] German Cancer Research Center (DKFZ), Division Signaling and Functional Genomics, Heidelberg, Germany.

[163 ] Copenhagen Lupus and Vasculitis Clinic, Section 4242 - Rigshospitalet, Copenhagen, Denmark.

[164 ] University of Copenhagen, Institute of Clinical Medicine, Copenhagen, Denmark.

[165 ] University of Maryland, Fischell Department of Bioengineering, College Park, MD, USA.

[166 ] Mayo Clinic, College of Medicine, Department of Physiology and Biomedical Engineering, Rochester, MN, USA.

[167 ] Department of Urology, Rotterdam, The Netherlands.

[168 ] University of Manchester, Division of Cancer Sciences, Manchester Cancer Research Centre, Manchester, UK.

[169 ] National Institutes of Health, National Cancer Institute, Center for Cancer Research, Bethesda, MD, USA.

[170 ] Children's Hospital of Los Angeles, Los Angeles, CA, USA.

[171 ] University of Southern California Keck School of Medicine, Los Angeles, CA, USA.

[172 ] City of Hope Comprehensive Cancer Center, Beckman Research Institute, Department of Molecular Medicine, Duarte, CA, USA.

[173 ] German Research Center for Environmental Health, Institute for Virology, Munich, Germany.

[174 ] University of Texas MD Anderson Cancer Center, Department of Cancer Biology, Metastasis Research Center, Houston, TX, USA.

[175 ] The Johns Hopkins University School of Medicine, Department of Psychiatry and Behavioral Sciences, Baltimore, MD, USA.

[176 ] National Institutes of Health, National Cancer Institute, Center for Cancer Research, Laboratory of Pathology, Bethesda, MD, USA.

[177 ] National Cancer Center Research Institute, Tokyo, Japan.

[178 ] University of Tsukuba, Tsukuba, Japan.

[179 ] University of Michigan, Biointerfaces Institute, Ann Arbor, MI, USA.

[180 ] University of Michigan, Department of Urology, Ann Arbor, MI, USA.

[181 ] École normale supérieure, Paris, France.

[182 ] Federal Research and Clinical Center of Physical-Chemical Medicine, Moscow, Russia.

[183 ] Oslo University Hospital, Department of Medical Biochemistry, Blood Cell Research Group, Oslo, Norway.

[184 ] Kyung Hee University, Department of Applied Chemistry, Yongin, Korea.

[185 ] Princess Margaret Cancer Centre, University Health Network, Toronto, Canada.

[186 ] University of Toronto, Department of Medical Biophysics, Toronto, Canada.

[187 ] Duke University, Department of Ophthalmology, Durham, NC, USA.

[188 ] West Virginia University, Department of Chemical and Biomedical Engineering and WVU Cancer Institute, Morgantown, WV, USA.

[189 ] West Virginia University, Department of Microbiology Immunology and Cell Biology, Morgantown, WV, USA.

[190 ] German Armed Forces Central Hospital, Department of General, Visceral and Thoracic Surgery, Koblenz, Germany.

[191 ] Saarland University Medical Center, Department of Medicine II, Homburg, Germany.

[192 ] University of Belgrade, Institute for the Application of Nuclear Energy, INEP, Belgrade, Serbia.

[193 ] University of Mainz, Institute of Developmental Biology and Neurobiology, Mainz, Germany.

[194 ] University Medical Center Hamburg-Eppendorf, Institute of Neuropathology, Hamburg, Germany.

[195 ] Hudson Institute of Medical Research, Melbourne, Australia.

[196 ] Central Research Laboratories, Sysmex Co., Kobe, Japan.

[197 ] Monash University, Melbourne, Australia.

[198 ] Hasselt University, Biomedical Research Institute (BIOMED), Hasselt, Belgium.

[199 ] Finnish Red Cross Blood Service, Research and Development, Helsinki, Finland.

[200 ] Cincinnati Cancer Center, Cincinnati, OH, USA.

[201 ] University of Cincinnati College of Medicine, Cincinnati, OH, USA.

[202 ] Thomas Jefferson University, Sidney Kimmel Medical School, Department of Cancer Biology, Philadelphia, PA, USA.

[203 ] University of Virginia, Flow Cytometry Core, School of Medicine, Charlottesville, VA, USA.

[204 ] University of California, San Diego, Department of Obstetrics, Gynecology, and Reproductive Sciences, La Jolla, CA, USA.

[205 ] AstraZeneca, Discovery Sciences, IMED Biotech Unit, Gothenburg, Sweden.

[206 ] Eulji University, School of Medicine, Daejeon, South Korea.

[207 ] Genome Institute of Singapore, ASTAR, Singapore.

[208 ] Federal University of Paraná, Department of Genetics, Human Molecular Genetics Laboratory, Curitiba, Brazil.

[209 ] University of Ljubljana, Faculty of Medicine, Institute of Biochemistry, Ljubljana, Slovenia.

[210 ] University of California, San Diego, Department of Pediatrics, San Diego, CA, USA.

[211 ] University of British Columbia Okanagan, Kelowna, Canada.

[212 ] University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Department of Medicine, Cambridge NIHR BRC Cell Phenotyping Hub, Cambridge, UK.

[213 ] Semmelweis University, Department of Physiology, Budapest, Hungary.

[214 ] Institute of Medical Biology (IMB), Agency for Science and Technology (ASTAR), Singapore.

[215 ] Latvian Biomedical Research and Study Centre, Riga, Latvia.

[216 ] Oslo University Hospital-The Norwegian Radium Hospital, Institute for Cancer Research, Department of Molecular Cell Biology, Oslo, Norway.

[217 ] Utrecht University, University Medical Center Utrecht, Center for Molecular Medicine & Regenerative Medicine Center, Utrecht, The Netherlands.

[218 ] Stellenbosch University, Department of Physiological Sciences, Stellenbosch, South Africa.

[219 ] Trinity College Dublin, School of Pharmacy and Pharmaceutical Sciences, Panoz Institute & Trinity Biomedical Sciences Institute, Dublin, Ireland.

[220 ] Harvard University, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

[221 ] Mossakowski Medical Research Centre, NeuroRepair Department, Warsaw, Poland.

[222 ] K.G. Jebsen Brain Tumor Research Centre, Department of Biomedicine, University of Bergen, Bergen, Norway.

[223 ] Utrecht University, University Medical Center Utrecht, Department of Neurosurgery, Brain Center Rudolf Magnus, Institute of Neurosciences, Utrecht, The Netherlands.

[224 ] Utrecht University, University Medical Center Utrecht, Department of Pathology, Utrecht, The Netherlands.

[225 ] Mayo Clinic, Rochester, MN, USA.

[226 ] Universitat de València, Departament de Farmàcia i Tecnologia Farmacèutica i Parasitologia, Àrea de Parasitologia, Valencia, Spain.

[227 ] Universitat de València, Health Research Institute La Fe, Joint Research Unit on Endocrinology, Nutrition and Clinical Dietetics, Valencia, Spain.

[228 ] Università degli Studi di Milano, Department of Clinical Sciences and Community Health, EPIGET LAB, Milan, Italy.

[229 ] A.C.Camargo Cancer Center, São Paulo, Brazil.

[230 ] University of Gothenburg, Sahlgrenska Academy, Department of Rheumatology and Inflammation Research, Gothenburg, Sweden.

[231 ] University of Southern California, Los Angeles, CA, USA.

[232 ] SickKids Hospital, Department of Anesthesia and Pain Medicine, Toronto, Canada.

[233 ] University of Toronto, Department of Anesthesia, Toronto, Canada.

[234 ] Florida State University College of Medicine, Department of Biomedical Sciences, Tallahassee, FL, USA.

[235 ] The School of Biomedical Sciences, University of Western Australia, Perth, Australia.

[236 ] University of Antwerp, Centre for Proteomics, Antwerp, Belgium.

[237 ] Georg-Speyer-Haus Institute for Tumor Biology and Experimental Therapy, Frankfurt, Germany.

[238 ] QIMR Berghofer Medical Research Institute, Herston, Australia.

[239 ] Aalborg University Hospital, Department of Clinical Immunology, Aalborg, Denmark.

[240 ] EVSEARCH.DK, Denmark.

[241 ] Erasmus MC, Rotterdam, The Netherlands.

[242 ] Namur Thrombosis and Hemostasis Center (NTHC), NARILIS, Namur, Belgium.

[243 ] Université Catholique de Louvain, CHU UCL Namur, Hematology-Hemostasis Laboratory, Yvoir, Belgium.

[244 ] University of Padova, Department of Women's and Children's Health, Padova, Italy.

[245 ] Brown University, Women and Infants Hospital, Providence, RI, USA.

[246 ] German Cancer Consortium (DKTK), Partner Site Freiburg and German Cancer Research Center (DKFZ), Heidelberg, Germany.

[247 ] Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Institute for Infection Prevention and Hospital Epidemiology, Freiburg, Germany.

[248 ] Aarhus University, Department of Clinical Medicine, Aarhus, Denmark.

[249 ] Sorbonne Université, Centre National de la Recherche Scientifique, Research Unit Biology of Adaptation and Aging (B2A), Team Compensation in Neurodegenerative and Aging (Brain-C), Paris, France.

[250 ] University of Pisa, Centro Dipartimentale di Biologia Cellulare Cardio-Respiratoria, Pisa, Italy.

[251 ] Universidade Federal do Rio de Janeiro, Instituto de Microbiologia, Rio de Janeiro, Brazil.

[252 ] National Institutes of Health, National Institute on Aging, Baltimore, MD, USA.

[253 ] University of Liège, GIGA-R(MBD), PSI Laboratory, Liège, Belgium.

[254 ] Queen Mary University of London, Blizard Institute, Epigenetics & Cellular Senescence Group, London, UK.

[255 ] National Cancer Center Research Institute, Division of Molecular and Cellular Medicine, Tokyo, Japan.

[256 ] McGill University, The Research Institute of the McGill University Health Centre, Montreal, Canada.

[257 ] IIS-Fundacion Jimenez Diaz-UAM, Department of Nephrology and Hypertension, Madrid, Spain.

[258 ] Spanish Kidney Research Network, REDINREN, Madrid, Spain.

[259 ] Universidad Autónoma de Madrid, School of Medicine, Department of Medicine, Madrid, Spain.

[260 ] Graduate School of Public Health at the University of Pittsburgh, Division of Occupational and Environmental Medicine, Pittsburgh, PA, USA.

[261 ] AstraZeneca, Discovery Sciences, IMED Biotech Unit, Cambridge, UK.

[262 ] Statens Serum Institut, Department of Autoimmunology and Biomarkers, Copenhagen, Denmark.

[263 ] University of Copenhagen, Faculty of Health and Medical Sciences, Novo Nordisk Foundation Center for Protein Research, Copenhagen, Denmark.

[264 ] University of Buenos Aires, Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Buenos Aires, Argentina.

[265 ] Amsterdam University Medical Centers, Department of Pathology, Amsterdam, The Netherlands.

[266 ] Spanish National Cancer Research Center (CNIO), Molecular Oncology Programme, Microenvironment and Metastasis Laboratory, Madrid, Spain.

[267 ] IRCCS - Istituto Ortopedico Rizzoli, Laboratory for Orthopaedic Pathophysiology and Regenerative Medicine, Bologna, Italy.

[268 ] The Scripps Research Institute-Scripps Florida, Department of Molecular Medicine, Jupiter, FL, USA.

[269 ] Radboud University Medical Center, Department of Rheumatology, Nijmegen, The Netherlands.

[270 ] Duke University Medical Center, Departments of Medicine and Immunology, Durham, NC, USA.

[271 ] Durham VAMC, Medical Research Service, Durham, NC, USA.

[272 ] Philipps University Marburg, Experimental Tumor Biology, Marburg, Germany.

[273 ] Pontificia Universidad Católica de Chile, Advanced Center for Chronic Diseases (ACCDiS), Santiago, Chile.

[274 ] Pontificia Universidad Católica de Chile, Faculty of Medicine, Department of Hematology-Oncology, Santiago, Chile.

[275 ] CNR Institute of Neuroscience, Milan, Italy.

[276 ] University of California, San Francisco, CA, USA.

[277 ] Veterans Affairs Medical Center, San Francisco, CA, USA.

[278 ] The Warren Alpert Medical School of Brown University, Department of Medicine, Providence, RI, USA.

[279 ] Department of Veterans Affairs, San Francisco, CA, USA.

[280 ] University of Palermo, Department of Biopathology and Medical Biotechnologies, Palermo, Italy.

[281 ] McGill University, Montreal, Canada.

[282 ] Instituto Oswaldo Cruz, Rio de Janeiro, Brazil.

[283 ] Universidade Federal de Paraná, Paraná, Brazil.

[284 ] Institut Curie, CNRS UMR144, PSL Research University, Paris, France.

[285 ] University of Michigan Medical School, Ann Arbor, MI, USA.

[286 ] Weizmann Institute of Science, Department of Biomolecular Sciences, Rehovot, Israel.

[287 ] University Medical Center Hamburg-Eppendorf, Department of Neurosurgery, Hamburg, Germany.

[288 ] University of Minnesota Medical School, Institute on the Biology of Aging and Metabolism, Department of Biochemistry, Molecular Biology and Biophysics, Minneapolis, MN, USA.

[289 ] CNC, Coimbra, Portugal.

[290 ] Paracelsus Medical University, Department of Transfusion Medicine, Salzburg, Austria.

[291 ] Spinal Cord Injury & Tissue Regeneration Center Salzburg (SCI-TReCS), Salzburg, Austria.

[292 ] University of Lyon, Lyon-Sud Faculty of Medicine, CarMeN Laboratory (UMR INSERM 1060-INRA 1397), Pierre-Bénite, France.

[293 ] Maastricht University, GROW, School for Oncology and Developmental Biology, Maastricht Radiation Oncology (MaastRO) Lab, Maastricht, The Netherlands.

[294 ] Sapienza University of Rome, Department of Experimental Medicine, Rome, Italy.

[295 ] West Virginia University, Morgantown, WV, USA.

[296 ] American Red Cross, Scientific Affairs, Gaithersburg, MD, USA.

[297 ] Icahn School of Medicine at Mount Sinai, Department of Medicine, Cardiology, New York City, NY, USA.

[298 ] Advanced Center for Chronic Diseases, Santiago, Chile.

[299 ] University of Chile, Faculty of Chemical and Pharmaceutical Science, Laboratory of Nanobiotechnology and Nanotoxicology, Santiago, Chile.

[300 ] Clínica las Condes, Extracellular Vesicles in Personalized Medicine Group, Santiago, Chile.

[301 ] Oregon Health & Science University, Department of Anesthesiology & Perioperative Medicine, Portland, OR, USA.

[302 ] Technische Universität Darmstadt, Department of Biology, Darmstadt, Germany.

[303 ] University Medical Center Utrecht, Laboratory for Clinical Chemistry & Hematology, Utrecht, The Netherlands.

[304 ] University of Toronto, Department of Medicine, Division of Neurology, Toronto, Canada.

[305 ] University of Bristol, Bristol, UK.

[306 ] University of California, Los Angeles, California NanoSystems Institute, Los Angeles, CA, USA.

[307 ] University of California, Los Angeles, Department of Pathology and Laboratory Medicine, Los Angeles, CA, USA.

[308 ] University of California, Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA.

[309 ] University of Gothenburg, Institute of Clinical Sciences, Department of Surgery, Sahlgrenska Cancer Center, Gothenburg, Sweden.

[310 ] Research Service, Olin E. Teague Veterans' Medical Center, Temple, TX, USA.

[311 ] Texas A&M University College of Medicine, Institute for Regenerative Medicine and Department of Molecular and Cellular Medicine, College Station, TX, USA.

[312 ] Cancer Institute of JFCR, Tokyo, Japan.

[313 ] University of Helsinki, EV Core Facility, Helsinki, Finland.

[314 ] University of Helsinki, Faculty of Biological and Environmental Sciences, Molecular and Integrative Biosciences Research Programme, EV group, Helsinki, Finland.

[315 ] INEB - Instituto de Engenharia Biomédica, Porto, Portugal.

[316 ] University of Porto, i3S-Instituto de Investigação e Inovação em Saúde, Porto, Portugal.

[317 ] University of Porto, ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Porto, Portugal.

[318 ] Maria Sklodowska-Curie Institute - Oncology Center, Gliwice Branch, Gliwice, Poland.

[319 ] Kansas State University, College of Veterinary Medicine, Manhattan, KS, USA.

[320 ] René Rachou Institute/FIOCRUZ, Belo Horizonte, Brazil.

[321 ] The University of Queensland, Brisbane, Australia.

[322 ] Washington University, Saint Louis, MO, USA.

[323 ] Harvard Medical School, Department of Medicine, Boston, MA, USA.

[324 ] Massachusetts General Cancer Center, Boston, MA, USA.

[325 ] FAU Erlangen-Nuremberg, Transfusion and Haemostaseology Department, Erlangen, Germany.

[326 ] University of Auckland, Department of Molecular Medicine and Pathology, Auckland, New Zealand.

[327 ] Hiroshima University, Institute of Biomedical & Health Sciences, Department of Cellular and Molecular Biology, Hiroshima, Japan.

[328 ] University of Michigan, Department of Biomedical Engineering, Ann Arbor, MI, USA.

[329 ] University of Michigan, Department of Internal Medicine - Hematology/Oncology Division, Ann Arbor, MI, USA.

[330 ] University of Manchester, Manchester, UK.

[331 ] Georgetown University, Department of Medicine, Washington, DC, USA.

[332 ] Sanjay Gandhi Postgraduate Institute of Medical Sciences, Department of Molecular Medicine & Biotechnology, Lucknow, India.

[333 ] National University of Singapore, Faculty of Dentistry, Singapore.

[334 ] INSERM U1068, Aix Marseille University, CNRS UMR7258, Marseille, France.

[335 ] UNIFESP, Departamento de Ciências Farmacêuticas, Diadema, Brazil.

[336 ] Institut Pasteur de Montevideo, Functional Genomics Unit, Montevideo, Uruguay.

[337 ] Universidad de la República, Faculty of Science, Nuclear Research Center, Analytical Biochemistry Unit, Montevideo, Uruguay.

[338 ] Beth Israel Deaconess Medical Center, Boston, MA, USA.

[339 ] University of Perugia, Department of Chemistry, Biology and Biotechnology, Perugia, Italy.

[340 ] University Medical Center Utrecht, Department of Nephrology and Hypertension, Utrecht, The Netherlands.

[341 ] TGen, Neurogenomics Division, Phoenix, AZ, USA.

[342 ] Center for Psychiatry and Neuroscience, INSERM U894, Paris, France.

[343 ] Department of Pathology, Erasmus MC, Erasmus Optical Imaging Centre, Rotterdam, The Netherlands.

[344 ] Mayo Clinic, Department of Orthopedic Surgery, Rochester, MN, USA.

[345 ] IPATIMUP, Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal.

[346 ] University of Porto, Faculty of Pharmacy (FFUP), Porto, Portugal.

[347 ] University of Kentucky, College of Medicine, Department of Physiology, Lexington, KY, USA.

[348 ] Universidade Federal do Rio Grande do Sul, Instituto de Ciências Básicas da Saúde, Departamento de Microbiologia, Imunologia e Parasitologia, Porto Alegre, Brazil.

[349 ] The Florey Institute of Neuroscience and Mental Health, Melbourne, Australia.

[350 ] The University of Melbourne, The Department of Medicine, Melbourne, Australia.

[351 ] UMR 7365 CNRS-Université de Lorraine, Vandœuvre-lès-Nancy, France.

[352 ] Oslo University Hospital Rikshospitalet, Research Institute of Internal Medicine, Oslo, Norway.

[353 ] Regional Research Network on Extracellular Vesicles, RRNEV, Oslo, Norway.

[354 ] University of Oslo, Institute of Clinical Medicine, Oslo, Norway.

[355 ] University of Gothenburg, The Sahlgrenska Academy, Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Mölndal, Sweden.

[356 ] Case Western Reserve University, Department of Medicine, Cleveland, OH, USA.

[357 ] University Hospitals Cleveland Medical Center, Department of Medicine, Cleveland, OH, USA.

[358 ] Vanderbilt University School of Medicine, Department of Cell and Developmental Biology, Nashville, TN, USA.

[359 ] Danube University Krems, Department for Biomedical Research and Christian Doppler Laboratory for Innovative Therapy Approaches in Sepsis, Krems an der Donau, Austria.

[360 ] University of Würzburg, Rudolf Virchow Center, Würzburg, Germany.

[361 ] The University of Vermont Medical Center, Department of Medicine, Burlington, VT, USA.

[362 ] University Hospital RWTH Aachen, Department of Thoracic and Cardiovascular Surgery, Aachen, Germany.

[363 ] Karolinska Institute, Department of Medicine and Center for Molecular Medicine, Respiratory Medicine Unit, Stockholm, Sweden.

[364 ] Chinese Academy of Sciences, Wenzhou Institute of Biomaterials and Engineering, Wenzhou, China.

[365 ] Houston Methodist Research Institute, Department of Nanomedicine, Houston, TX, USA.

[366 ] Mayo Clinic, Department of Transplantation Medicine/Department of Physiology and Biomedical Engineering, Jacksonville, FL, USA.

[367 ] George Papanicolaou Hospital, Public Cord Blood Bank, Department of Haematology - BMT Unit, Thessaloniki, Greece.

[368 ] Universidade Federal de São Paulo Campus Diadema, Departamento de Ciências Farmacêuticas, Laboratório de Imunologia Celular e Bioquímica de Fungos e Protozoários, São Paulo, Brazil.

[369 ] Xiamen University, Department of Chemical Biology, Xiamen, China.

[370 ] Centro de Biología Molecular Severo Ochoa, Instituto de Investigación Sanitaria la Princesa (IIS-IP), Madrid, Spain.

[371 ] Universidad Autónoma de Madrid, Departamento de Biología Molecular, Madrid, Spain.

[372 ] Tsinghua University, School of Pharmaceutical Sciences, Beijing, China.

[373 ] Technical University Eindhoven, Faculty Biomedical Technology, Eindhoven, The Netherlands.

[374 ] University of Padova, Department of Comparative Biomedicine and Food Science, Padova, Italy.

[375 ] Institute of Physiology CAS, Department of Biomaterials and Tissue Engineering, BIOCEV, Vestec, Czech Republic.

[376 ] Institute of Physiology CAS, Department of Biomaterials and Tissue Engineering, Prague, Czech Republic.

[377 ] University of California, Los Angeles, Department of Bioengineering, Los Angeles, CA, USA.

[378 ] Vilnius University, Institute of Biomedical Sciences, Department of Physiology, Biochemistry, Microbiology and Laboratory Medicine, Vilnius, Lithuania.

[379 ] Guangzhou Medical University, School of Pharmaceutical Sciences & the Fifth Affiliated Hospital, Key Laboratory of Molecular Target & Clinical Pharmacology, Guangzhou, China.

[380 ] Karolinska Institute, Clinical Research Center, Unit for Molecular Cell and Gene Therapy Science, Stockholm, Sweden.

[381 ] Aix-Marseille Université, Institut Paoli-Calmettes, INSERM U1068, CNRS UMR7258, Centre de Recherche en Cancérologie de Marseille, Marseille, France.

[382 ] KU Leuven (Leuven University), Department of Human Genetics, Leuven, Belgium.

[383 ] University of California, Davis, Department of Nutrition, Davis, CA, USA.

[384 ] Exosomics Siena SpA, Siena, Italy.

Article

Publisher Item ID: 1535750

DOI: 10.1080/20013078.2018.1535750

PMC ID: 6322352

PubMed ID: 30637094

SO-VID: 5b60b780-768f-4334-9573-22d3c3f9dd43

History

Keywords: ectosomes,exosomes,extracellular vesicles,guidelines,microparticles,microvesicles,minimal information requirements,reproducibility,rigor,standardization

Data availability:

Keywords: ectosomes, exosomes, extracellular vesicles, guidelines, microparticles, microvesicles, minimal information requirements, reproducibility, rigor, standardization

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.

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