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

Journal of extracellular vesicles - Tập 7 Số 1 - 2018
Clotilde Théry1, Kenneth W. Witwer2,3, Elena Aïkawa4,5, María José Alcaraz6, Johnathon D. Anderson7, Ramaroson Andriantsitohaina8, Anna Antoniou9,10, Tanina Arab11, Fabienne Archer12, Georgia K. Atkin‐Smith13, D. Craig Ayre14,15, Jean‐Marie Bach16, Daniel Bachurski17, Hossein Baharvand18,19, Leonora Balaj20, Shawn Baldacchino21, Natalie Bauer22, Amy A. Baxter13, Mary Bebawy23, Carla Beckham24, Apolonija Bedina Zavec25, Abderrahim Benmoussa26, Anna C. Berardi27, Paolo Bergese28,29,30, Ewa Bielska31, Cherie Blenkiron32, Sylwia Bobis‐Wozowicz33, Éric Boilard26, Wilfrid Boireau34, Antonella Bongiovanni35, Francesc E. Borràs36,37,38, Steffi Bösch16, Chantal M. Boulanger39,40, Xandra O. Breakefield41, Andrew Breglio42,43, Meadhbh Á. Brennan44,45,46, David R. Brigstock47,48, Alain Brisson49, Marike L. D. Broekman50,51,52, Jacqueline Bromberg53,54, Paulina Bryl‐Górecka55, Shilpa Buch56, Amy H. Buck57, Dylan Burger58,59,60, Sara Busatto61,30, Dominik Buschmann62, Benedetta Bussolati63, Edit I. Buzás64,65, James Brian Byrd66, Giovanni Camussi67, David R. F. Carter68, Sarah Caruso13, Lawrence W. Chamley69, Yu‐Ting Chang70, Chihchen Chen71,72, Daiwen Chen73, Lesley Cheng13, Aled Clayton74, Stefano Piatto Clerici75, Alex Cocks74, Emanuele Cocucci76,77, Anabela Cordeiro‐da‐Silva78, Yvonne Couch79, Frank A. W. Coumans80, Beth Coyle81, Rossella Crescitelli82, Miriã Ferreira Criado83, Crislyn D’Souza‐Schorey84, Saumya Das85, Amrita Datta Chaudhuri2, Paola de Candia86, Eliezer F De Santana87, Olivier De Wever88,89, Hernando A. del Portillo90,91,92, Tanguy Demaret93, Sarah Deville94,95, Andrew Devitt96, Bert Dhondt88,97,98, Dolores Di Vizio99, Lothar C. Dieterich100, Vincenza Dolo101, Ana Paula Domínguez Rubio102, Massimo Dominici103,104, Maurício Rocha Dourado105,106, Tom A. P. Driedonks107, Filipe V. Duarte108, Heather M. Duncan109,110, Ramon M. Eichenberger111, Karin M. Ekström112, Samir EL Andaloussi113,114, Céline Elie-Caille34, Uta Erdbrügger115, Juan Manuel Falcón‐Pérez116,117, Farah Fatima118, Jason E. Fish119,120, Miguel Flores‐Bellver121, András Försönits122, Annie Frelet-Barrand34, Fabia Fricke123,124, Gregor Fuhrmann125,126,127, Susanne Gabrielsson128, Ana Gámez‐Valero36,129, Chris Gardiner130, Kathrin Gärtner131, Raphaël Gaudin132,133, Yong Song Gho134, Bernd Giebel135, Caroline Gilbert26, Mario Gimona136, Ilaria Giusti101, Deborah C. I. Goberdhan137, André Görgens138,139,135, Sharon M. Gorski140,141, David W. Greening13, Julia Christina Gross142,143, Alice Gualerzi144, Gopal N. Gupta145, Dakota Gustafson120, Aase Handberg146,147, Reka A. Haraszti148, Paul Harrison149,150, Hargita Hegyesi122, An Hendrix88,89, Andrew F. Hill13, Fred H. Hochberg151,152, Karl F. Hoffmann153, Beth Holder154,155, Harry Holthöfer156, Baharak Hosseinkhani157, Guoku Hu56, Yiyao Huang158,3, Veronica Huber159, Stuart Hunt160, Ahmed Ibrahim161, Tsuneya Ikezu162, Jameel M. Inal163, Mustafa Işın164, Alena Ivanova165, Hannah K Jackson81, Søren Jacobsen166,167, Steven M. Jay168, Muthuvel Jayachandran169, Guido Jenster170, Lanzhou Jiang13, Suzanne M. Johnson171, Jennifer Jones172, Ambrose Jong173,173, Tijana Jovanović‐Talisman174, Stephanie Jung175, Raghu Kalluri176, Shin‐ichi Kano177, Sukhbir Kaur178, Yumi Kawamura179,180, Evan T. Keller181,182, Delaram Khamari122, Elena Khomyakova183,184, Anastasia Khvorova148, Peter Kierulf185, Kwang Pyo Kim186, Thomas Kislinger187,188, Mikael Klingeborn189, David J. Klinke190,191, Miroslaw Kornek192,193, Maja Kosanović194, Árpád Ferenc Kovács122, Eva‐Maria Krämer‐Albers195, Susanne Krasemann196, Mirja Krause197, Igor V. Kurochkin198, Gina D. Kusuma199,200, Sören Kuypers201, Saara Laitinen202, Scott M. Langevin203,204, Lucia R. Languino205, Joanne Lannigan206, Cecilia Lässer82, Louise C. Laurent207, Grégory Lavieu1, Elisa Lázaro‐Ibáñez208, Soazig Le Lay8, Myung‐Shin Lee209, Fiona Lee210, Débora S. Lemos211, Metka Lenassi212, Aleksandra Leszczynska213, Isaac T. S. Li214, Ke Liao56, Sten F.W.M. Libregts215, Erzsébet Ligeti216, Rebecca Lim199,200, Sai Kiang Lim217, Aija Linē218, Karen Linnemannstöns142,143, Alicia Llorente219, Catherine Lombard93, Magdalena J. Lorenowicz220, Ákos M. Lőrincz216, Jan Lötvall82, Jason Lovett221, Michelle C. Lowry222, Xavier Loyer39,40, Quan Lu223, Barbara Łukomska224, Taral R. Lunavat225, Sybren L. N. Maas226,227, Harmeet Malhi228, Antonio Marcilla229,230, Jacopo Mariani231, Javier Mariscal99, Elena S. Martens‐Uzunova170, Lorena Martín‐Jaular1, Dominique Meyer8, Vilma R. Martins232, Mathilde Mathieu1, Suresh Mathivanan13, Marco Maugeri233, Lynda K. McGinnis234, Mark J. McVey235,236, David G. Meckes237, Katie Meehan238, Inge Mertens239,95, Valentina R. Minciacchi240, Andreas Möller241, Maléne Møller Jørgensen242,243, Aizea Morales‐Kastresana172, Jess Morhayim244, François Mullier245,246, Maurizio Muraca247, Luca Musante115, Veronika Mussack62, Dillon C. Muth3, Kathryn H. Myburgh221, Tanbir Najrana248, Muhammad Nawaz233, Irina Nazarenko249,250, Peter Nejsum251, Christian Néri252, Tommaso Neri253, Rienk Nieuwland80, Leonardo Nimrichter254, John P. Nolan255, Esther Nm Nolte-'t Hoen107, Nicole Noren Hooten256, Lorraine O’Driscoll222, Tina O’Grady257, Ana O’Loghlen258, Takahiro Ochiya259, Martin Olivier260, Alberto Ortíz261,262,263, Luis A. Ortiz264, Xabier Osteikoetxea265, Ole Østergaard266,267, Matías Ostrowski268, Jaesung Park134, D. Michiel Pegtel269, Héctor Peinado270, Francesca Perut271, Michael W. Pfaffl62, Donald G. Phinney272, Bartijn C. H. Pieters273, Ryan Pink68, David S. Pisetsky274,275, Elke Pogge von Strandmann276, Iva Polakovičová277,278, Ivan K. H. Poon13, Bonita H. Powell3, Ilaria Prada279, Lynn Pulliam280,281, Peter J. Quesenberry282, Annalisa Radeghieri283,30, Robert L. Raffaı̈284,285, Stefania Raimondo286, Janusz Rak260,287, Marcel I. Ramirez288,289, Graça Raposo290, Morsi S Rayyan291, Neta Regev‐Rudzki292, Franz Ricklefs293, Paul D. Robbins294, David D. Roberts178, Sílvia C. Rodrigues295,108, Eva Rohde136,296,297, Sophie Rome298, Kasper M.A. Rouschop299, Aurelia Rughetti300, Ashley E. Russell301, Paula Saá302, Susmita Sahoo303,304, Edison Salas‐Huenuleo305,306, Catherine Sánchez307, Julie A. Saugstad308, Meike J. Saul309, Raymond M. Schiffelers310, Raphaël Schneider120,311, Tine Hiorth Schøyen3, Aaron Scott312, Eriomina Shahaj159, Shivani Sharma313,314,315, Olga Shatnyeva208, Faezeh Shekari316, Ganesh Vilas Shelke82,317, Ashok K. Shetty318,319, Kiyotaka Shiba320, Pia Siljander321,322, Andreia Silva323,324,325, Agata Skowronek326, Orman L. Snyder327, Rodrigo Pedro Soares328, Barbara W. Sódar122, Carolina Soekmadji329,330, Javier Sotillo111, Philip D. Stahl331, Willem Stoorvogel107, Shannon L. Stott332,333, Erwin Strasser334, Simon Swift335, Hidetoshi Tahara336, Muneesh Tewari337,338,182, Kate Timms339, Swasti Tiwari340,341, Rochelle Tixeira13, Mercedes Tkach1, Wei Seong Toh342, Richard Tomasini343, Ana Cláudia Torrecilhas344, Juan Pablo Tosar345,346, Vasilis Toxavidis347, Lorena Urbanelli348, Pieter Vader310, Bas W. M. van Balkom349, Susanne G van der Grein107, Jan Van Deun88,89, Martijn J. C. van Herwijnen107, Kendall Van Keuren‐Jensen350, Guillaume van Niel351, Martin E. van Royen352, André J. van Wijnen353, M. Helena Vasconcelos354,355,325, Ivan J. Vechetti356, Tiago Degani Veit357, Laura J. Vella358,359, Émilie Velot360, Frederik J. Verweij351, Beate Vestad361,362,363, Jose Luis Viñas58,59,60, Tamás Visnovitz122, Krisztina V. Vukman122, Jessica Wahlgren364, Dionysios C. Watson365,366, Marca H. M. Wauben107, Alissa M. Weaver367, Jason Webber74, Viktoria Weber368, Ann M. Wehman369,370, Daniel J. Weiss371, Joshua A Welsh172, Sebastian Wendt372, Åsa M. Wheelock373, Zoltán Wiener122, Leonie Witte142,143, Joy Wolfram374,375,376, Angeliki Xagorari377, Patrícia Xander378, Jing Xu140,141, Xiaomei Yan379, María Yáñez‐Mó380,381, Hang Yin382, Yuana Yuana383, Valentina Zappulli384, Jana Zárubová385,386,387, Vytautas Žėkas388, Jianye Zhang389, Zezhou Zhao3, Lei Zheng390, Alexander R. Zheutlin291, Antje M. Zickler391,392, Pascale Zimmermann393,394, Angela M. Zivkovic395, Davide Zocco396, Ewa Zuba‐Surma33
1Institut Curie, INSERM U932, PSL Research University, Paris, France
2The Johns Hopkins University School of Medicine Department of Neurology Baltimore MD USA
3The Johns Hopkins University School of Medicine, Department of Molecular and Comparative Pathobiology, Baltimore, MD, USA
4Brigham and Women's Hospital Center for Interdisciplinary Cardiovascular Sciences Boston MA USA
5Harvard Medical School Cardiovascular Medicine Boston MA USA
6Interuniversity Research Institute for Molecular Recognition and Technological Development (IDM), University of Valencia, Polytechnic University of Valencia, Valencia, Spain
7University of California, Davis, Department of Otolaryngology, Davis, CA, USA
8INSERM U1063 Université d'Angers CHU d'Angers Angers France
9German Centre for Neurodegenerative Diseases (DZNE), Bonn, Germany; University Hospital Bonn (UKB), Bonn, Germany
10University Hospital Bonn (UKB), Bonn, Germany
11Université de Lille INSERM, U‐1192 Laboratoire Protéomique Réponse Inflammatoire et Spectrométrie de Masse ‐ PRISM Lille France
12University of Lyon, INRA, EPHE, UMR754 Viral Infections and Comparative Pathology, Lyon, France
13La Trobe University, La Trobe Institute for Molecular Science, Department of Biochemistry and Genetics, Bundoora, Australia
14Atlantic Cancer Research Institute, Moncton, Canada
15Atlantic Cancer Research Institute, Moncton, Canada; Mount Allison University, Department of Chemistry and Biochemistry, Sackville, Canada
16Université Bretagne Loire Oniris INRA IECM Nantes France
17University of Cologne, Department of Internal Medicine I, Cologne, Germany
18Royan Institute for Stem Cell Biology and Technology, ACECR, Cell Science Research Center, Department of Stem Cells and Developmental Biology, Tehran, Iran; University of Science and Culture, ACECR, Department of Developmental Biology, Tehran, Iran
19University of Science and Culture ACECR Department of Developmental Biology Tehran Iran
20Massachusetts General Hospital, Department of Neurosurgery, Boston, MA, USA
21University of Malta, Department of Pathology, Msida, Malta
22University of South Alabama, Department of Pharmacology, Center for Lung Biology, Mobile, AL, USA
23University of Technology Sydney, Discipline of Pharmacy, Graduate School of Health, Sydney, Australia
24University of Rochester, Rochester, NY USA
25National Institute of Chemistry, Department of Molecular Biology and Nanobiotechnology, Ljubljana, Slovenia
26Université Laval Centre de Recherche du CHU de Québec Department of Infectious Diseases and Immunity Quebec City Canada
27Ospedale Santo Spirito, Pescara, Italy
28CSGI - Research Center for Colloids and Nanoscience, Florence, Italy; INSTM - National Interuniversity Consortium of Materials Science and Technology, Florence, Italy; University of Brescia, Department of Molecular and Translational Medicine, Brescia, Italy
29INSTM ‐ National Interuniversity Consortium of Materials Science and Technology Florence Italy
30University of Brescia, Department of Molecular and Translational Medicine, Brescia, Italy
31University of Birmingham, Institute of Microbiology and Infection, Birmingham, UK
32University of Auckland, Auckland, New Zealand
33Jagiellonian University Faculty of Biochemistry, Biophysics and Biotechnology Department of Cell Biology Kraków Poland
34FEMTO‐ST Institute UBFC CNRS ENSMM UTBM Besançon France
35Institute of Biomedicine and Molecular Immunology (IBIM), National Research Council (CNR) of Italy, Palermo, Italy
36Germans Trias i Pujol Research Institute (IGTP) Can Ruti Campus REMAR‐IVECAT Group Badalona Spain
37Germans Trias i Pujol University Hospital Nephrology Service Badalona Spain
38Universitat Autònoma de Barcelona Department of Cell Biology, Physiology & Immunology Barcelona Spain
39INSERM UMR‐S 970 Paris Cardiovascular Research Center Paris France
40Université Paris Descartes, Sorbonne Paris Cité, Paris, France
41Massachusetts General Hospital and Neuroscience Program, Harvard Medical School, Department of Neurology and Radiology, Boston, MA, USA
42Icahn School of Medicine at Mount Sinai, New York City, NY, USA; National Institutes of Health, National Institute on Deafness and Other Communication Disorders, Bethesda, MD, USA
43National Institutes of Health National Institute on Deafness and Other Communication Disorders Bethesda MD USA
44Harvard University, School of Engineering and Applied Sciences, Cambridge, MA, USA
45Massachusetts General Hospital Harvard Medical School Department of Neurology Boston MA USA
46Université de Nantes INSERM UMR 1238 Bone Sarcoma and Remodeling of Calcified Tissues PhyOS Nantes France
47Nationwide Children's Hospital, Columbus, OH, USA;
48The Ohio State University, Columbus, OH, USA.
49UMR‐CBMN CNRS‐Université de Bordeaux Bordeaux France
50Haaglanden Medical Center, Department of Neurosurgery, The Hague, The Netherlands; Leiden University Medical Center, Department of Neurosurgery, Leiden, The Netherlands; Massachusetts General Hospital, Department of Neurology, Boston, MA, USA
51Leiden University Medical Center, Department of Neurosurgery, Leiden, The Netherlands
52Massachusetts General Hospital, Department of Neurology, Boston, MA, USA
53Memorial Sloan Kettering Cancer Center, Department of Medicine, New York City, NY, USA; Weill Cornell Medicine, Department of Medicine, New York City, NY, USA
54Weill Cornell Medicine Department of Medicine New York City NY USA
55Lund University, Department of Cardiology, Lund, Sweden
56University of Nebraska Medical Center, Department of Pharmacology and Experimental Neuroscience, Omaha, NE, USA
57University of Edinburgh Institute of Immunology & Infection Research Edinburgh UK
58Kidney Research Centre, Ottawa, Canada; Ottawa Hospital Research Institute, Ottawa, Canada; University of Ottawa, Ottawa, Canada
59Ottawa Hospital Research Institute, Ottawa, Canada
60University of Ottawa, Ottawa, Canada
61Mayo Clinic, Department of Transplantation, Jacksonville, FL, USA; University of Brescia, Department of Molecular and Translational Medicine, Brescia, Italy
62Technical University of Munich, TUM School of Life Sciences Weihenstephan, Division of Animal Physiology and Immunology, Freising, Germany
63University of Torino, Department of Molecular Biotechnology and Health Sciences, Torino, Italy
64MTA-SE Immuno-Proteogenomics Research Groups, Budapest, Hungary; Semmelweis University, Department of Genetics, Cell- and Immunobiology, Budapest, Hungary
65Semmelweis University Department of Genetics, Cell‐ and Immunobiology Budapest Hungary
66University of Michigan, Department of Medicine, Ann Arbor, MI, USA
67University of Torino,Department of Medical Sciences,Torino,Italy
68Oxford Brookes University, Department of Biological and Medical Sciences, Oxford, UK
69University of Auckland, Department of Obstetrics and Gynaecology, Auckland, New Zealand
70National Taiwan University Hospital, Department of Internal Medicine, Taipei, Taiwan
71National Tsing Hua University Institute of Nanoengineering and Microsystems Hsinchu Taiwan
72National Tsing Hua University, Department of Power Mechanical Engineering, Hsinchu, Taiwan
73Leibniz Institute for Farm Animal Biology (FBN), Institute of Reproductive Biology, Dummerstorf, Germany
74Cardiff University School of Medicine, Cardiff, UK
75UNICAMP, Institute of Biology, Campinas, Brazil
76The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA
77The Ohio State University, College of Pharmacy, Division of Pharmaceutics and Pharmaceutical Chemistry, Columbus, OH, USA
78University of Porto, Faculty of Pharmacy (FFUP), IBMC/I3S, Porto, Portugal
79University of Oxford, Radcliffe Department of Medicine, Acute Stroke Programme - Investigative Medicine, Oxford, UK
80Academic Medical Centre of the University of Amsterdam, Department of Clinical Chemistry and Vesicle Observation Centre, Amsterdam, The Netherlands
81The University of Nottingham School of Medicine Children's Brain Tumour Research Centre Nottingham UK
82University of Gothenburg, Institute of Medicine at Sahlgrenska Academy, Krefting Research Centre, Gothenburg, Sweden
83University of São Paulo, Ribeirão Preto Medical School, Ribeirão Preto, Brazil
84University of Notre Dame, Department of Biological Sciences, Notre Dame, IN ,USA
85Massachusetts General Hospital, Boston, MA, USA
86IRCCS MultiMedica, Milan, Italy
87The Sociedade Beneficente Israelita Brasileira Albert Einstein São Paulo Brazil
88Cancer Research Institute Ghent, Ghent, Belgium
89Cancer Research Institute Ghent, Ghent, Belgium; Ghent University, Department of Radiation Oncology and Experimental Cancer Research, Laboratory of Experimental Cancer Research, Ghent, Belgium
90ISGlobal Hospital Clínic ‐ Universitat de Barcelona PVREX Group Barcelona Spain
91Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain
92Institut d'Investigació Germans Trias i Pujol (IGTP) PVREX group Badalona Spain
93Université Catholique de Louvain, Institut de Recherche Expérimentale et Clinique (IREC), Laboratory of Pediatric Hepatology and Cell Therapy, Brussels, Belgium
94Universiteit Hasselt, Diepenbeek, Belgium; Vlaamse Instelling voor Technologisch Onderzoek (VITO), Mol, Belgium
95Vlaamse Instelling voor Technologisch Onderzoek (VITO), Mol, Belgium
96Aston University School of Life & Health Sciences Birmingham UK
97Cancer Research Institute Ghent, Ghent, Belgium; Ghent University Hospital, Department of Urology, Ghent, Belgium; Ghent University, Department of Radiation Oncology and Experimental Cancer Research, Laboratory of Experimental Cancer Research, Ghent, Belgium
98Ghent University Department of Radiation Oncology and Experimental Cancer Research Laboratory of Experimental Cancer Research Ghent Belgium
99Cedars-Sinai Medical Center, Los Angeles, CA, USA
100ETH Zurich, Institute of Pharmaceutical Sciences, Zurich, Switzerland
101University of l'Aquila, Department of Life, Health and Environmental Sciences, l'Aquila, Italy
102Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales, Departamento de Química Biológica, Buenos Aires, Argentina
103TPM of Mirandola, Mirandola, Italy; University of Modena and Reggio Emilia, Division of Oncology, Modena, Italy
104University of Modena and Reggio Emilia Division of Oncology Modena Italy
105University of Campinas, Piracicaba Dental School, Department of Oral Diagnosis, Piracicaba, Brazil; University of Oulu, Faculty of Medicine, Cancer and Translational Medicine Research Unit, Oulu, Finland
106University of Oulu Faculty of Medicine, Cancer and Translational Medicine Research Unit Oulu Finland
107Utrecht University Faculty of Veterinary Medicine Department of Biochemistry and Cell Biology Utrecht The Netherlands
108Exogenus Therapeutics Cantanhede Portugal
109McGill University The Research Institute of the McGill University Health Centre Child Health and Human Development Program Montreal Canada
110McGill University, Division of Experimental Medicine, Montreal, Canada; McGill University, The Research Institute of the McGill University Health Centre, Child Health and Human Development Program, Montreal, Canada
111James Cook University, Australian Institute of Tropical Health and Medicine, Centre for Biodiscovery and Molecular Development of Therapeutics, Cairns, Australia
112University of Gothenburg, Institute of Clinical Sciences at Sahlgrenska Academy, Department of Biomaterials, Gothenburg, Sweden
113Evox Therapeutics Limited, Oxford, UK; Karolinska Institute, Stockholm, Sweden
114Karolinska Institute, Stockholm, Sweden.
115University of Virginia Health System, Department of Medicine, Division of Nephrology, Charlottesville, VA, USA
116CIC bioGUNE, CIBERehd, Exosomes Laboratory & Metabolomics Platform, Derio, Spain; IKERBASQUE Research Science Foundation, Bilbao, Spain
117IKERBASQUE Research Science Foundation Bilbao Spain
118University of São Paulo Ribeirão Preto Medical School Department of Pathology and Forensic Medicine Ribeirão Preto Brazil
119Toronto General Hospital Research Institute, University Health Network, Toronto, Canada; University of Toronto, Department of Laboratory Medicine and Pathobiology, Toronto, Canada
120University of Toronto, Department of Laboratory Medicine and Pathobiology, Toronto, Canada
121University of Colorado, School of Medicine, Department of Ophthalmology, Cell Sight-Ocular Stem Cell and Regeneration Program, Aurora, CO, USA
122Semmelweis University, Department of Genetics, Cell- and Immunobiology, Budapest, Hungary
123German Cancer Research Center (DKFZ), Clinical Cooperation Unit Applied Tumor Biology, Heidelberg, Germany; University Hospital Heidelberg, Institute of Pathology, Applied Tumor Biology, Heidelberg, Germany
124University Hospital Heidelberg Institute of Pathology, Applied Tumor Biology Heidelberg Germany
125Helmholtz Centre for Infection Research, Braunschweig, Germany
126Helmholtz Institute for Pharmaceutical Research Saarland, Saarbrücken, Germany
127Saarland University, Saarbrücken, Germany
128Karolinska Institute, Department of Medicine Solna, Division for Immunology and Allergy, Stockholm, Sweden
129Universitat Autònoma de Barcelona Hospital Universitari and Health Sciences Research Institute Germans Trias i Pujol Department of Pathology Barcelona Spain
130University College London, London, UK
131Helmholtz Center Munich German Research Center for Environmental Health, Research Unit Gene Vectors, Munich, Germany
132Inserm, U1110, Strasbourg, France
133Université de Strasbourg, Strasbourg, France
134POSTECH (Pohang University of Science and Technology), Department of Life Sciences, Pohang, South Korea
135University Hospital Essen University Duisburg‐Essen Institute for Transfusion Medicine Essen Germany
136Paracelsus Medical University GMP Unit Salzburg Austria
137University of Oxford, Department of Physiology, Anatomy and Genetics, Oxford, UK
138Evox Therapeutics Limited, Oxford, UK; Karolinska Institute, Clinical Research Center, Department of Laboratory Medicine, Stockholm, Sweden; University Hospital Essen, University Duisburg-Essen, Institute for Transfusion Medicine, Essen, Germany
139Karolinska Institute Clinical Research Center Department of Laboratory Medicine Stockholm Sweden
140BC Cancer Canada's Michael Smith Genome Sciences Centre Vancouver Canada
141BC Cancer Canada's Michael Smith Genome Sciences Centre Vancouver Canada; Simon Fraser University, Department of Molecular Biology and Biochemistry, Burnaby, Canada
142University Medical Center Göttingen Developmental Biochemistry Göttingen Germany
143University Medical Center Göttingen Hematology and Oncology Göttingen Germany
144IRCCS Fondazione Don Carlo Gnocchi, Laboratory of Nanomedicine and Clinical Biophotonics (LABION), Milan, Italy
145Loyola University Chicago, Department of Urology, Maywood, IL, USA
146Aalborg University Clinical Institute Aalborg Denmark
147Aalborg University Hospital, Department of Clinical Biochemistry, Aalborg, Denmark; Aalborg University, Clinical Institute, Aalborg, Denmark
148University of Massachusetts Medical School, RNA Therapeutics Institute, Worcester, MA, USA
149Psychiatry (United Kingdom)
150University of Birmingham, Birmingham, UK
151Scintillon Institute, La Jolla, CA, USA; University of California, San Diego, Department of Neurosurgery, La Jolla, CA, USA
152University of California, San Diego Department of Neurosurgery La Jolla CA USA
153Aberystwyth University, Institute of Biological, Environmental and Rural Sciences (IBERS), Aberystwyth, United Kingdom
154Imperial College London, London, UK; MRC The Gambia, Fajara, The Gambia
155MRC The Gambia Fajara The Gambia
156University Clinic Eppendorf, Hamburg, Germany
157Hasselt University, Biomedical Research Institute (BIOMED), Department of Medicine and Life Sciences, Hasselt, Belgium
158Nanfang Hospital, Southern Medical University, Department of Clinical Laboratory Medicine, Guangzhou, China; The Johns Hopkins University School of Medicine, Department of Molecular and Comparative Pathobiology, Baltimore, MD, USA
159Fondazione IRCCS Istituto Nazionale dei Tumori, Unit of Immunotherapy of Human Tumors, Milan, Italy
160The University of Sheffield, Sheffield, UK
161Cedars-Sinai Medical Center, Smidt Heart Institute, Los Angeles, CA, USA
162Boston University School of Medicine, Boston, MA, USA
163University of Hertfordshire, School of Life and Medical Sciences, Biosciences Research Group, Hatfield, UK
164Istanbul University Oncology Institute, Basic Oncology Department, Istanbul, Turkey
165German Cancer Research Center (DKFZ), Division Signaling and Functional Genomics, Heidelberg, Germany
166Copenhagen Lupus and Vasculitis Clinic, Section 4242 - Rigshospitalet, Copenhagen, Denmark; University of Copenhagen, Institute of Clinical Medicine, Copenhagen, Denmark
167University of Copenhagen Institute of Clinical Medicine Copenhagen Denmark
168University of Maryland, Fischell Department of Bioengineering, College Park, MD, USA
169Mayo Clinic, College of Medicine, Department of Physiology and Biomedical Engineering, Rochester, MN, USA
170Department of Urology, Rotterdam, The Netherlands
171University of Manchester, Division of Cancer Sciences, Manchester Cancer Research Centre, Manchester, UK
172National Institutes of Health, National Cancer Institute, Center for Cancer Research, Bethesda, MD, USA
173University of Southern California Keck School of Medicine, Los Angeles, CA, USA.
174City of Hope Comprehensive Cancer Center, Beckman Research Institute, Department of Molecular Medicine, Duarte, CA, USA
175German Research Center for Environmental Health, Institute for Virology, Munich, Germany
176University of Texas MD Anderson Cancer Center, Department of Cancer Biology, Metastasis Research Center, Houston, TX, USA
177The Johns Hopkins University School of Medicine, Department of Psychiatry and Behavioral Sciences, Baltimore, MD, USA
178National Institutes of Health, National Cancer Institute, Center for Cancer Research, Laboratory of Pathology, Bethesda, MD, USA
179National Cancer Center Research Institute, Tokyo, Japan; University of Tsukuba, Tsukuba, Japan
180University of Tsukuba, Tsukuba, Japan
181University of Michigan, Department of Urology, Ann Arbor, MI, USA
182University of Michigan, Biointerfaces Institute, Ann Arbor, MI, USA
183Federal Research and Clinical Center of Physical–Chemical Medicine, Moscow, Russia
184École Normale Supérieure, Paris, France
185Oslo University Hospital, Department of Medical Biochemistry, Blood Cell Research Group, Oslo, Norway
186Kyung Hee University, Department of Applied Chemistry, Yongin, Korea
187Princess Margaret Cancer Centre, University Health Network, Toronto, Canada; University of Toronto, Department of Medical Biophysics, Toronto, Canada
188University of Toronto Department of Medical Biophysics Toronto Canada
189Duke University, Department of Ophthalmology, Durham, NC, USA
190West Virginia University Department of Microbiology Immunology and Cell Biology Morgantown WV USA
191West Virginia University, Department of Chemical and Biomedical Engineering and WVU Cancer Institute, Morgantown, WV, USA
192German Armed Forces Central Hospital, Department of General, Visceral and Thoracic Surgery, Koblenz, Germany; Saarland University Medical Center, Department of Medicine II, Homburg, Germany
193Saarland University Medical Center Department of Medicine II Homburg Germany
194University of Belgrade, Institute for the Application of Nuclear Energy – INEP, Belgrade, Serbia
195Department of Biology, Molecular Cell Biology, University of Mainz (D-55128 Mainz - Germany)
196University Medical Center Hamburg-Eppendorf, Institute of Neuropathology, Hamburg, Germany
197Hudson Institute of Medical Research, Melbourne, Australia
198Central Research Laboratories, Sysmex Co., Kobe, Japan
199Hudson Institute of Medical Research, Melbourne, Australia; Monash University, Melbourne, Australia
200Monash University, Melbourne, Australia
201Hasselt University, Biomedical Research Institute (BIOMED), Hasselt, Belgium
202Finnish Red Cross Blood Service, Research and Development, Helsinki, Finland
203Cincinnati Cancer Center, Cincinnati, OH, USA; University of Cincinnati College of Medicine, Cincinnati, OH, USA
204University of Cincinnati College of Medicine, Cincinnati, OH USA
205Thomas Jefferson University, Sidney Kimmel Medical School, Department of Cancer Biology, Philadelphia, PA, USA
206University of Virginia, Flow Cytometry Core, School of Medicine, Charlottesville, VA, USA
207University of California, San Diego, Department of Obstetrics, Gynecology, and Reproductive Sciences, La Jolla, CA, USA
208AstraZeneca, Discovery Sciences, IMED Biotech Unit, Gothenburg, Sweden
209Eulji University School of Medicine, Daejeon, South Korea
210Genome Institute of Singapore, A*STAR, Singapore
211Federal University of Paraná Department of Genetics Human Molecular Genetics Laboratory Curitiba Brazil
212University of Ljubljana, Faculty of Medicine, Institute of Biochemistry, Ljubljana, Slovenia
213University of California San Diego, Department of Pediatrics, San Diego, CA, USA
214University of British Columbia (Okanagan), Kelowna, Canada
215University of Cambridge School of Clinical Medicine Addenbrooke's Hospital Department of Medicine Cambridge NIHR BRC Cell Phenotyping Hub Cambridge UK
216Semmelweis University Department of Physiology, Budapest, Hungary
217Institute of Medical Biology (IMB), Agency for Science and Technology (A*STAR), Singapore
218Latvian Biomedical Research and Study Centre, Riga, Latvia
219Oslo University Hospital-The Norwegian Radium Hospital, Institute for Cancer Research, Department of Molecular Cell Biology, Oslo, Norway
220Utrecht University, University Medical Center Utrecht, Center for Molecular Medicine & Regenerative Medicine Center, Utrecht, The Netherlands
221Stellenbosch University, Department of Physiological Sciences, Stellenbosch, South Africa
222Trinity College Dublin, School of Pharmacy and Pharmaceutical Sciences, Panoz Institute & Trinity Biomedical Sciences Institute, Dublin, Ireland
223Harvard University, Harvard T.H. Chan School of Public Health, Boston, MA, USA
224Mossakowski Medical Research Centre, NeuroRepair Department, Warsaw, Poland
225K.G. Jebsen Brain Tumor Research Centre, Department of Biomedicine, University of Bergen, Bergen, Norway
226Utrecht University University Medical Center Utrecht Department of Pathology Utrecht The Netherlands
227Utrecht University, University Medical Center Utrecht, Department of Neurosurgery, Brain Center Rudolf Magnus, Institute of Neurosciences, Utrecht, The Netherlands
228Mayo Clinic, Rochester, MN USA
229Universitat de València Departament de Farmàcia i Tecnologia Farmacèutica i Parasitologia Àrea de Parasitologia Valencia Spain
230Universitat de València Health Research Institute La Fe, Joint Research Unit on Endocrinology, Nutrition and Clinical Dietetics Valencia Spain
231Università degli Studi di Milano Department of Clinical Sciences and Community Health EPIGET LAB Milan Italy
232A.C.Camargo Cancer Center, São Paulo, Brazil
233University of Gothenburg, Sahlgrenska Academy, Department of Rheumatology and Inflammation Research, Gothenburg, Sweden
234University of Southern California, Los Angeles, CA USA
235SickKids Hospital, Department of Anesthesia and Pain Medicine, Toronto, Canada; University of Toronto, Department of Anesthesia, Toronto, Canada
236University of Toronto, Department of Anesthesia, Toronto, Canada
237Florida State University College of Medicine, Department of Biomedical Sciences, Tallahassee, FL, USA
238The School of Biomedical Sciences, University of Western Australia, Perth, Australia
239University of Antwerp, Centre for Proteomics, Antwerp, Belgium; Vlaamse Instelling voor Technologisch Onderzoek (VITO), Mol, Belgium
240Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, Frankfurt, Germany
241QIMR Berghofer Medical Research Institute, Herston, Australia
242Aalborg University Hospital Department of Clinical Immunology Aalborg Denmark
243Aalborg University Hospital, Department of Clinical Immunology, Aalborg, Denmark; EVSEARCH.DK, Denmark
244Erasmus MC, Rotterdam, The Netherlands
245Namur Thrombosis and Hemostasis Center (NTHC) NARILIS Namur Belgium
246Université Catholique de Louvain CHU UCL Namur Hematology‐Hemostasis Laboratory Yvoir Belgium
247University of Padova, Department of Women's and Children's Health, Padova, Italy
248Brown University, Women and Infants Hospital, Providence, RI, USA
249German Cancer Consortium (DKTK), Partner Site Freiburg and German Cancer Research Center (DKFZ), Heidelberg, Germany; Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Institute for Infection Prevention and Hospital Epidemiology, Freiburg, Germany
250Medical Center ‐ University of Freiburg Faculty of Medicine University of Freiburg Institute for Infection Prevention and Hospital Epidemiology Freiburg Germany
251Aarhus University Department of Clinical Medicine Aarhus Denmark
252Sorbonne 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
253University of Pisa, Centro Dipartimentale di Biologia Cellulare Cardio-Respiratoria, Pisa, Italy
254Universidade Federal do Rio de Janeiro, Instituto de Microbiologia, Rio de Janeiro, Brazil
255Scintillon Institute, La Jolla, CA, USA
256National Institutes of Health, National Institute on Aging, Baltimore, MD, USA
257University of Liège GIGA‐R(MBD) PSI Laboratory Liège Belgium
258Queen Mary University of London, Blizard Institute, Epigenetics & Cellular Senescence Group, London, UK
259National Cancer Center Research Institute, Division of Molecular and Cellular Medicine, Tokyo, Japan
260McGill University, The Research Institute of the McGill University Health Centre, Montreal, Canada
261IIS‐Fundacion Jimenez Diaz‐UAM Department of Nephrology and Hypertension Madrid Spain
262Spanish Kidney Research Network (REDINREN), Madrid, Spain
263Universidad Autónoma de Madrid School of Medicine Department of Medicine Madrid Spain
264Graduate School of Public Health at the University of Pittsburgh Division of Occupational and Environmental Medicine Pittsburgh PA USA
265AstraZeneca, Discovery Sciences, IMED Biotech Unit, Cambridge, UK
266Statens Serum Institut, Department of Autoimmunology and Biomarkers, Copenhagen, Denmark; University of Copenhagen, Faculty of Health and Medical Sciences, Novo Nordisk Foundation Center for Protein Research, Copenhagen, Denmark
267University of Copenhagen Faculty of Health and Medical Sciences Novo Nordisk Foundation Center for Protein Research Copenhagen Denmark
268University of Buenos Aires Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS) Buenos Aires Argentina
269Amsterdam University Medical Centers, Department of Pathology, Amsterdam, The Netherlands
270Spanish National Cancer Research Center (CNIO), Molecular Oncology Programme, Microenvironment and Metastasis Laboratory, Madrid, Spain
271IRCCS - Istituto Ortopedico Rizzoli, Laboratory for Orthopaedic Pathophysiology and Regenerative Medicine, Bologna, Italy
272The Scripps Research Institute‐Scripps Florida Department of Molecular Medicine Jupiter FL USA
273Radboud University Medical Center, Department of Rheumatology, Nijmegen, The Netherlands
274Duke University Medical Center, Departments of Medicine and Immunology, Durham, NC, USA; Durham VAMC, Medical Research Service, Durham, NC, USA
275Durham VAMC Medical Research Service Durham NC USA
276Philipps University Marburg, Experimental Tumor Biology, Marburg, Germany
277Pontificia Universidad Católica de Chile Advanced Center for Chronic Diseases (ACCDiS) Santiago Chile
278Pontificia Universidad Católica de Chile Faculty of Medicine Department of Hematology‐Oncology Santiago Chile
279CNR, Institute of Neuroscience, Milan, Italy
280University of California, San Francisco, CA, USA; Veterans Affairs Medical Center, San Francisco, CA, USA
281Veterans Affairs Medical Center, San Francisco, CA USA
282The Warren Alpert Medical School of Brown University, Department of Medicine, Providence, RI, USA
283CSGI - Research Center for Colloids and Nanoscience, Florence, Italy; University of Brescia, Department of Molecular and Translational Medicine, Brescia, Italy
284Department of Veterans Affairs, San Francisco, CA, USA; University of California, San Francisco, CA, USA
285University of California San Francisco, CA. USA
286University of Palermo Department of Biopathology and Medical Biotechnologies Palermo Italy
287McGill University, Montreal, Canada; McGill University, The Research Institute of the McGill University Health Centre, Montreal, Canada
288Instituto Oswaldo Cruz, Rio de Janeiro, Brazil
289Universidade Federal de Paraná Paraná Brazil
290Institut Curie, CNRS UMR144, PSL Research University, Paris, France
291University of Michigan Medical School, Ann Arbor, MI USA
292Weizmann Institute of Science, Department of Biomolecular Sciences, Rehovot, Israel
293University Medical Center Hamburg-Eppendorf, Department of Neurosurgery, Hamburg, Germany
294University of Minnesota Medical School, Institute on the Biology of Aging and Metabolism, Department of Biochemistry, Molecular Biology and Biophysics, Minneapolis, MN, USA
295CNC, Coimbra, Portugal; Exogenus Therapeutics, Cantanhede, Portugal
296Paracelsus Medical University, Department of Transfusion Medicine, Salzburg, Austria
297Spinal Cord Injury & Tissue Regeneration Center Salzburg (SCI‐TReCS) Salzburg Austria
298University of Lyon Lyon‐Sud Faculty of Medicine CarMeN Laboratory (UMR INSERM 1060‐INRA 1397) Pierre‐Bénite France
299Maastricht University, GROW, School for Oncology and Developmental Biology, Maastricht Radiation Oncology (MaastRO) Lab, Maastricht, The Netherlands
300Sapienza University of Rome, Department of Experimental Medicine, Rome, Italy
301West Virginia University, Morgantown WV, USA
302American Red Cross, Scientific Affairs, Gaithersburg, MD, USA
303Cardiovascular Research Center (Boston - United States)
304Icahn School of Medicine at Mount Sinai Department of Medicine, Cardiology New York City NY USA
305Advanced Center for Chronic Diseases, Santiago, Chile; University of Chile, Faculty of Chemical and Pharmaceutical Science, Laboratory of Nanobiotechnology and Nanotoxicology, Santiago, Chile
306University of Chile Faculty of Chemical and Pharmaceutical Science Laboratory of Nanobiotechnology and Nanotoxicology Santiago Chile
307Clínica las Condes Extracellular Vesicles in Personalized Medicine Group Santiago Chile
308Oregon Health & Science University Department of Anesthesiology & Perioperative Medicine Portland OR USA
309Technische Universität Darmstadt Department of Biology Darmstadt Germany
310University Medical Center Utrecht Laboratory for Clinical Chemistry & Hematology Utrecht The Netherlands
311University of Toronto Department of Medicine Division of Neurology Toronto Canada
312University of Bristol, Bristol, UK
313University of California, Los Angeles Department of Pathology and Laboratory Medicine Los Angeles CA USA
314University of California, Los Angeles Jonsson Comprehensive Cancer Center Los Angeles CA USA
315University of California, Los Angeles, California NanoSystems Institute, Los Angeles, CA, USA
316Royan Institute for Stem Cell Biology and Technology, ACECR, Cell Science Research Center, Department of Stem Cells and Developmental Biology, Tehran, Iran
317University of Gothenburg, Institute of Clinical Sciences, Department of Surgery, Sahlgrenska Cancer Center, Gothenburg, Sweden
318Texas A&M University College of Medicine, Institute for Regenerative Medicine and Department of Molecular and Cellular Medicine, College Station, TX, USA
319Texas A&M University College of Medicine Institute for Regenerative Medicine and Department of Molecular and Cellular Medicine College Station TX USA
320Cancer Institute of JFCR, Tokyo, Japan
321University of Helsinki Faculty of Biological and Environmental Sciences, Molecular and Integrative Biosciences Research Programme, EV group Helsinki Finland
322University of Helsinki, EV Core Facility, Helsinki, Finland
323INEB, Instituto de Engenharia Biomédica, Porto, Portugal
324University of Porto ICBAS ‐ Instituto de Ciências Biomédicas Abel Salazar Porto Portugal
325University of Porto i3S‐Instituto de Investigação e Inovação em Saúde Porto Portugal
326Maria Sklodowska-Curie Institute - Oncology Center, Gliwice Branch, Gliwice, Poland
327Kansas State University, College of Veterinary Medicine, Manhattan, KS, USA
328René Rachou Institute/FIOCRUZ Belo Horizonte Brazil
329QIMR Berghofer Medical Research Institute, Herston, Australia; The University of Queensland, Brisbane, Australia
330The University of Queensland, Brisbane, Australia
331Washington University, Saint Louis, MO, USA
332Harvard Medical School, Department of Medicine, Boston, MA, USA; Massachusetts General Cancer Center, Boston, MA, USA
333Massachusetts General Cancer Center Boston MA USA
334FAU Erlangen-Nuremberg, Transfusion and Haemostaseology Department, Erlangen, Germany
335University of Auckland Department of Molecular Medicine and Pathology, Auckland, New Zealand
336Hiroshima University, Institute of Biomedical & Health Sciences, Department of Cellular and Molecular Biology, Hiroshima, Japan
337University of Michigan, Department of Biomedical Engineering, Ann Arbor, MI, USA
338University of Michigan Department of Internal Medicine ‐ Hematology/Oncology Division Ann Arbor MI USA
339University of Manchester, Manchester, UK
340Georgetown University, Department of Medicine, Washington, DC, USA; Sanjay Gandhi Postgraduate Institute of Medical Sciences, Department of Molecular Medicine & Biotechnology, Lucknow, India
341Sanjay Gandhi Postgraduate Institute of Medical Sciences Department of Molecular Medicine & Biotechnology Lucknow India
342National University of Singapore, Faculty of Dentistry, Singapore
343INSERM U1068, Aix Marseille University, CNRS UMR7258, Marseille, France
344UNIFESP Departamento de Ciências Farmacêuticas Diadema Brazil
345Institut Pasteur de Montevideo Functional Genomics Unit Montevideo Uruguay
346Universidad de la República Faculty of Science Nuclear Research Center Analytical Biochemistry Unit Montevideo Uruguay
347Beth Israel Deaconess Medical Center, Boston, MA, USA.
348University of Perugia, Department of Chemistry, Biology and Biotechnology, Perugia, Italy
349University Medical Center Utrecht, Department of Nephrology and Hypertension, Utrecht, The Netherlands
350TGen, Neurogenomics Division, Phoenix, AZ, USA
351Center for Psychiatry and Neuroscience, INSERM U894, Paris, France
352Department of Pathology, Erasmus MC, Erasmus Optical Imaging Centre, Rotterdam, The Netherlands
353Mayo Clinic, Department of Orthopedic Surgery, Rochester, MN, USA
354IPATIMUP, Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal
355University of Porto Faculty of Pharmacy (FFUP) Porto Portugal
356University of Kentucky, College of Medicine, Department of Physiology, Lexington, KY, USA
357Universidade Federal do Rio Grande do Sul Instituto de Ciências Básicas da Saúde Departamento de Microbiologia, Imunologia e Parasitologia Porto Alegre Brazil
358The Florey Institute of Neuroscience and Mental Health, Melbourne, Australia; The University of Melbourne, The Department of Medicine, Melbourne, Australia
359The University of Melbourne The Department of Medicine Melbourne Australia
360UMR 7365 CNRS‐Université de Lorraine Vandœuvre‐lès‐Nancy France
361Oslo University Hospital Rikshospitalet, Research Institute of Internal Medicine, Oslo, Norway; Regional Research Network on Extracellular Vesicles, RRNEV, Oslo, Norway; University of Oslo, Institute of Clinical Medicine, Oslo, Norway
362Regional Research Network on Extracellular Vesicles, RRNEV Oslo Norway
363University of Oslo, Institute of Clinical Medicine, Oslo, Norway
364University of Gothenburg The Sahlgrenska Academy Institute of Neuroscience and Physiology Department of Psychiatry and Neurochemistry Mölndal Sweden
365Case Western Reserve University Department of Medicine Cleveland OH USA
366Case Western Reserve University, Department of Medicine, Cleveland, OH, USA; University Hospitals Cleveland Medical Center, Department of Medicine, Cleveland, OH, USA
367Vanderbilt University School of Medicine, Department of Cell and Developmental Biology, Nashville, TN, USA
368Danube University Krems, Department for Biomedical Research and Christian Doppler Laboratory for Innovative Therapy Approaches in Sepsis, Krems an der Donau, Austria
369Department of Physiology (San Francisco, CA - United States)
370University of Würzburg Rudolf Virchow Center Würzburg Germany
371The University of Vermont Medical Center, Department of Medicine, Burlington, VT, USA
372University Hospital RWTH Aachen, Department of Thoracic and Cardiovascular Surgery, Aachen, Germany
373Karolinska Institute, Department of Medicine and Center for Molecular Medicine, Respiratory Medicine Unit, Stockholm, Sweden
374Chinese Academy of Sciences, Wenzhou Institute of Biomaterials and Engineering, Wenzhou, China; Houston Methodist Research Institute, Department of Nanomedicine, Houston, TX, USA; Mayo Clinic, Department of Transplantation Medicine/Department of Physiology and Biomedical Engineering, Jacksonville, FL, USA
375Houston Methodist Research Institute Department of Nanomedicine Houston TX USA
376Mayo Clinic Department of Transplantation Medicine/Department of Physiology and Biomedical Engineering Jacksonville FL USA
377George Papanicolaou Hospital, Public Cord Blood Bank, Department of Haematology - BMT Unit, Thessaloniki, Greece
378Universidade Federal de São Paulo Campus Diadema Departamento de Ciências Farmacêuticas Laboratório de Imunologia Celular e Bioquímica de Fungos e Protozoários São Paulo Brazil
379SDAU - Shandong Agricultural University (Daizong Road No.61,Taian,Shandong,China - China)
380Centro de Biología Molecular Severo Ochoa Instituto de Investigación Sanitaria la Princesa (IIS‐IP) Madrid Spain
381Universidad Autónoma de Madrid, Departamento de Biología Molecular, Madrid, Spain
382Institute of Chinese Medical Sciences - State Key Laboratory of Quality Research in Chinese Medicine Taipa, Macau SAR, (University of Macau, Taipa, Macau SAR - China)
383Technical University Eindhoven, Faculty Biomedical Technology, Eindhoven, The Netherlands
384University of Padova, Department of Comparative Biomedicine and Food Science, Padova, Italy
385Institute of Physiology CAS Department of Biomaterials and Tissue Engineering Prague Czech Republic
386Institute of Physiology CAS, Department of Biomaterials and Tissue Engineering, BIOCEV, Vestec, Czech Republic; University of California, Los Angeles, Department of Bioengineering, Los Angeles, CA, USA
387University of California, Los Angeles Department of Bioengineering Los Angeles CA USA
388Vilnius University, Institute of Biomedical Sciences, Department of Physiology, Biochemistry, Microbiology and Laboratory Medicine, Vilnius, Lithuania
389Guangzhou Medical University School of Pharmaceutical Sciences & the Fifth Affiliated Hospital Key Laboratory of Molecular Target & Clinical Pharmacology Guangzhou China
390Nanfang Hospital, Southern Medical University, Department of Clinical Laboratory Medicine, Guangzhou, China
391Human Genetics (Ulm - Germany)
392Karolinska Institute Clinical Research Center Unit for Molecular Cell and Gene Therapy Science Stockholm Sweden
393Aix‐Marseille Université Institut Paoli‐Calmettes INSERM U1068 CNRS UMR7258 Centre de Recherche en Cancérologie de Marseille Marseille France
394KU Leuven (Leuven University) Department of Human Genetics Leuven Belgium
395University of California, Davis, Department of Nutrition, Davis, CA, USA
396Exosomics Siena SpA, Siena, Italy

Tóm tắt

ABSTRACTThe 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.

Từ khóa


Tài liệu tham khảo

References especially those provided to illustrate methods and approaches are representative only and are not meant to be a comprehensive review of the literature. Most references were derived from suggestions provided in the MISEV2018 Survey results. Each reference was checked by multiple authors. Citation implies deemed relevance of scientific content and not an endorsement by the authors or ISEV of any particular journal or editorial practice.

10.3402/jev.v3.26913

10.1080/20013078.2017.1396823

Stein JM, 1991, Ectocytosis caused by sublytic autologous complement attack on human neutrophils. The sorting of endogenous plasma‐membrane proteins and lipids into shed vesicles, Biochem J, 274, 381, 10.1042/bj2740381

10.1016/j.tcb.2015.01.004

10.3402/jev.v2i0.20389

10.3402/jev.v5.32945

Rojas A, 2017, The imperative authentication of cell lines, Antimicrob Agents Chemother, 61, e01823, 10.1128/AAC.01823-17

ReidY StortsD RissT et al.Authentication of human cell lines by STR DNA profiling analysis [Internet].Assay Guidance Manual.2004. Available from:http://www.ncbi.nlm.nih.gov/pubmed/23805434

10.1186/1479-5876-9-47

10.1016/j.canlet.2009.03.041

10.1007/s00281-010-0228-6

10.2174/1568009615666150225121508

10.1111/acel.12734

10.1002/btm2.10065

10.1096/fj.201700417R

Klingeborn M, 2017, Directional exosome proteomes reflect polarity‐specific functions in retinal pigmented epithelium monolayers, Sci Rep, 7, 4901, 10.1038/s41598-017-05102-9

Mittelbrunn M, 2015, Organizing polarized delivery of exosomes at synapses, Traffic, 16, 327, 10.1111/tra.12258

10.1053/gast.2001.26263

10.1074/mcp.M112.021303

10.1007/978-1-4939-7652-2_4

10.1080/20013078.2018.1442088

10.1016/j.drudis.2018.03.006

Mitchell MD, 2015, Placental exosomes in normal and complicated pregnancy, Am J Obstet Gynecol, 213, S173, 10.1016/j.ajog.2015.07.001

10.3402/jev.v1i0.18396

10.1016/j.bbrc.2015.03.074

10.1080/20013078.2017.1302705

Taylor J, 2017, Calcium‐calpain dependent pathways regulate vesiculation in malignant breast cells, Curr Cancer Drug Targets, 17, 486, 10.2174/1568009616666161026165736

10.4049/jimmunol.180.7.5028

10.1096/fj.07-8079com

10.18632/oncotarget.11111

Saari H, 2015, Microvesicle‐ and exosome‐mediated drug delivery enhances the cytotoxicity of paclitaxel in autologous prostate cancer cells, J Control Release, 220, 727, 10.1016/j.jconrel.2015.09.031

10.1080/20013078.2017.1354645

10.1016/j.jprot.2014.07.020

10.1007/s10561-017-9617-6

10.1371/journal.pone.0036138

10.1189/jlb.0507277

10.1074/mcp.M900152-MCP200

10.1007/s00125-017-4331-2

10.1074/jbc.M117.802629

10.1210/jc.2015-2270

10.1038/s41598-017-08392-1

10.1152/ajprenal.00078.2017

10.1016/j.jcyt.2017.01.001

Saury C, 2018, Human serum and platelet lysate are appropriate xeno‐free alternatives for clinical‐grade production of human MuStem cell batches, Stem Cell Res Ther, 9, 128, 10.1186/s13287-018-0852-y

10.3402/jev.v4.26883

10.1016/j.imlet.2014.10.019

10.3402/jev.v4.26373

10.1002/0471143030.cb0322s30

10.1182/blood-2013-02-478925

10.1080/20013078.2017.1422674

10.1038/srep31175

10.3402/jev.v3.24783

10.1080/20013078.2016.1272832

10.1016/j.matbio.2014.05.007

10.3402/jev.v2i0.20360

10.1080/20013078.2017.1286095

10.1016/j.jim.2016.08.007

10.1186/1471-2121-14-23

Mullier F, 2013, Pre‐analytical issues in the measurement of circulating microparticles: current recommendations and pending questions, J Thromb Haemost

10.1111/j.1538-7836.2011.04610.x

10.1161/CIRCRESAHA.117.309417

10.1160/TH10-09-0595

10.3402/jev.v4.29260

Robbins PD, 2017, Extracellular vesicles and aging, Stem Cell Investig, 4, 98, 10.21037/sci.2017.12.03

10.1371/journal.pone.0144678

10.1016/j.bbrc.2016.07.073

10.1002/cyto.a.22892

10.1016/j.thromres.2013.11.010

10.1038/srep32651

10.1371/journal.pone.0064795

10.1016/j.jim.2014.06.007

10.1016/j.thromres.2010.12.014

10.1182/blood.V94.11.3791

10.1002/cpim.17

10.1073/pnas.1705206114

10.1016/j.placenta.2004.04.004

10.1111/j.1365-2567.2012.03568.x

10.1074/jbc.M112.404467

10.1080/20013078.2017.1348885

10.2337/db09-0216

10.4049/jimmunol.181.8.5242

10.1002/oby.20679

10.1161/CIRCRESAHA.117.311326

10.1161/CIRCULATIONAHA.108.816710

Michaelis ML, 2017, Methods in molecular biology, 107

10.1038/sj.ki.5000273

Vila‐Liante V, 2016, Impact of sample processing on the measurement of circulating microparticles: storage and centrifugation parameters, Clin Chem Lab Med, 54, 1759, 10.1515/cclm-2016-0036

Kriebardis AG, 2016, Microparticles variability in fresh frozen plasma: preparation protocol and storage time effects, Blood Transfus, 14, 228

10.3402/jev.v3.25465

Bosch S, 2016, Trehalose prevents aggregation of exosomes and cryodamage, Sci Rep, 6, 36162, 10.1038/srep36162

10.1080/20013078.2017.1359478

10.1186/s12885-016-2783-2

10.1208/s12248-017-0160-y

10.1097/MBC.0b013e32831be9c5

10.3402/jev.v4.30087

Reiner AT, 2017, Concise review: developing best‐practice models for the therapeutic use of extracellular vesicles, Stem Cells Transl Med, 6, 10.1002/sctm.17-0055

10.1080/20013078.2018.1473707

10.1016/j.colsurfb.2017.06.047

10.1038/s41598-017-01731-2

10.1038/s41598-017-10646-x

10.3402/jev.v4.27269

10.1038/s41598-017-02599-y

10.3402/jev.v4.27031

10.1186/scrt465

10.1080/20013078.2017.1294368

10.1016/j.chroma.2014.10.026

Heinemann ML, 2017, Methods in molecular biology, 33

10.1038/s41467-017-01196-x

10.1016/S0022-1759(02)00330-7

10.1186/1479-5876-3-10

10.1016/j.aca.2009.01.015

10.1038/s41556-018-0040-4

10.1021/acs.analchem.6b04634

10.1021/acs.langmuir.5b00095

10.1021/acsnano.7b02277

10.1021/acsnano.7b00549

10.1021/acsnano.7b08199

10.1021/nn506538f

10.1016/j.chroma.2014.04.093

10.1016/j.nano.2017.03.011

10.3402/jev.v4.27378

10.2144/000114575

10.1038/s41598-018-24163-y

10.1073/pnas.1522297113

10.1002/prca.200800093

10.3402/jev.v5.29254

10.1002/cyto.a.22644

10.1038/srep39846

10.1158/0008-5472.CAN-16-2942

10.1038/nnano.2016.134

10.1002/cbic.201402058

10.1371/journal.pone.0110443

10.1038/srep10266

10.1021/acs.analchem.7b04861

10.1080/20013078.2018.1435138

10.1002/pros.23393

10.1038/srep33935

10.1080/20013078.2017.1369805

10.3402/jev.v5.29828

Gallart‐Palau X, 2015, Extracellular vesicles are rapidly purified from human plasma by PRotein Organic Solvent PRecipitation (PROSPR), Sci Rep, 5, 14664, 10.1038/srep14664

Shin H, 2015, High‐yield isolation of extracellular vesicles using aqueous two‐phase system, Sci Rep, 5, 13103, 10.1038/srep13103

10.1128/JVI.02251-16

Musante L, 2014, A simplified method to recover urinary vesicles for clinical applications, and sample banking, Sci Rep, 4, 7532, 10.1038/srep07532

10.1016/j.biopen.2017.02.004

10.1039/C7LC00592J

10.1073/pnas.1709210114

10.1039/B916199F

10.1038/srep46224

10.1038/s41598-017-08826-w

10.1126/sciadv.1701133

10.1039/C5LC01117E

10.1039/c3lc41343h

10.1038/s41467-017-02261-1

10.3402/jev.v3.23430

10.1186/s12967-017-1374-6

10.1371/journal.pone.0136133

10.3402/jev.v3.25011

Livshits MA, 2015, Isolation of exosomes by differential centrifugation: theoretical analysis of a commonly used protocol, Sci Rep, 5, 17319, 10.1038/srep17319

10.1021/nn402232g

10.1007/978-1-4939-7652-2_7

10.1038/nmeth.4185

10.1016/j.jim.2008.03.001

10.1038/ki.2011.1

10.1111/jth.13514

10.1016/j.neo.2015.11.011

10.1152/ajplung.00369.2015

10.1038/ncomms8439

10.1038/nprot.2012.065

10.1111/j.1538-7836.2012.04683.x

10.3402/jev.v4.25530

10.1021/acsnano.7b07782

10.1080/20013078.2018.1454776

Nolan JP, 2013, A trigger channel threshold artifact in nanoparticle analysis, Cytometry A, 83, 301, 10.1002/cyto.a.22255

10.1111/jth.12554

10.1111/jth.12767

10.1016/j.jconrel.2014.12.041

Vrij J, 2013, Quantification of nanosized extracellular membrane vesicles with scanning ion occlusion sensing, Nanomedicine (Lond)

10.1016/j.bios.2016.08.100

10.1111/jth.14154

10.1111/j.1538-7836.2010.04074.x

10.1007/978-1-4939-7253-1_13

10.1080/20013078.2017.1388731

10.1111/jth.12602

10.1016/j.nano.2011.04.003

10.3402/jev.v2i0.19671

10.1371/journal.pone.0121184

10.1080/20013078.2017.1401897

10.1016/j.bbamem.2016.12.005

10.1093/nar/gkr254

10.1073/pnas.1019055108

10.1038/ncb2210

10.1002/ijc.29664

Suárez H, 2017, A bead‐assisted flow cytometry method for the semi‐quantitative analysis of extracellular vesicles, Sci Rep, 7, 11271, 10.1038/s41598-017-11249-2

10.3402/jev.v5.29975

10.1016/j.bios.2017.01.063

10.1038/s41551-016-0021

10.1021/ac500931f

10.3402/jev.v2i0.19861

10.1021/ac504861d

10.1016/j.scr.2009.12.003

10.3402/jev.v3.23111

10.1016/j.ejps.2016.09.008

10.18632/oncotarget.3598

10.18632/oncotarget.3801

10.3402/jev.v5.32570

10.1021/acs.analchem.5b02586

10.1080/20013078.2017.1305677

10.1073/pnas.1521230113

10.1016/j.ymeth.2015.04.008

10.1038/srep22519

10.3402/jev.v5.33109

10.1038/srep24316

10.1007/s00018-018-2773-4

10.1021/pr200901p

10.1371/journal.pone.0037279

10.3402/jev.v3.24858

10.1016/j.celrep.2016.03.085

10.1016/j.ccell.2014.09.005

Buck AH, 2014, Exosomes secreted by nematode parasites transfer small RNAs to mammalian cells and modulate innate immunity, Nat Commun, 5, 5488, 10.1038/ncomms6488

10.15252/embj.201696003

10.3402/jev.v4.26048

10.1373/clinchem.2016.271049

10.1021/ac5023056

10.1021/acs.chemrev.7b00534

10.1016/j.plipres.2017.03.001

10.1016/j.bbalip.2013.10.004

10.3402/jev.v3.20795

10.1182/blood-2003-03-0871

Gualerzi A, 2017, Raman spectroscopy uncovers biochemical tissue‐related features of extracellular vesicles from mesenchymal stromal cells, Sci Rep, 7, 9820, 10.1038/s41598-017-10448-1

10.1016/j.pupt.2016.05.003

10.1373/clinchem.2017.278978

Ullal AJ, 2010, Use of SYTO 13, a fluorescent dye binding nucleic acids, for the detection of microparticles in in vitro systems, Cytometry A, 77, 294, 10.1002/cyto.a.20833

10.1073/pnas.1704862114

10.3402/jev.v2i0.20677

Nolte‐'t Hoen EN, 2012, Deep sequencing of RNA from immune cell‐derived vesicles uncovers the selective incorporation of small non‐coding RNA biotypes with potential regulatory functions, Nucleic Acids Res, 10.1093/nar/gks658

10.1038/ncomms3980

10.1093/nar/gku347

10.1093/nar/gkv432

10.3402/jev.v4.26760

Li K, 2018, Advances, challenges, and opportunities in extracellular RNA biology: insights from the NIH exRNA strategic workshop, JCI Insight, 3

Chen M, 2016, Transcriptome and long noncoding RNA sequencing of three extracellular vesicle subtypes released from the human colon cancer LIM1863 cell line, Sci Rep, 6, 38397, 10.1038/srep38397

10.1038/ncomms8029

Ter‐Ovanesyan D, 2017, Imaging of isolated extracellular vesicles using fluorescence microscopy, Methods Mol Biol, 1660, 233, 10.1007/978-1-4939-7253-1_19

10.1039/C5AN00688K

Linares R, 2015, High‐speed centrifugation induces aggregation of extracellular vesicles, J Extracell Vesicles, 4, 29509, 10.3402/jev.v4.29509

10.3402/jev.v4.28680

10.1021/nn901824n

10.1080/20013078.2017.1359479

10.1021/acsami.6b09442

Mehdiani A, 2015, An innovative method for exosome quantification and size measurement, J Vis Exp, 95, 50974

10.3402/jev.v1i0.19179

10.1021/acs.analchem.7b00017

10.3402/jev.v4.28533

10.1002/cyto.a.22787

10.1080/09537104.2017.1280602

10.1021/acs.analchem.5b01636

10.1083/jcb.201506084

10.1021/ac501801m

10.1038/ncb2502

10.1002/cyto.a.22494

Headland SE, 2014, Cutting‐edge analysis of extracellular microparticles using ImageStream(X) imaging flow cytometry, Sci Rep, 4, 5237, 10.1038/srep05237

10.1021/acsnano.7b07060

10.1109/JSTQE.2011.2180516

10.1371/journal.pone.0179728

10.1111/jth.14009

Cvjetkovic A, 2016, Detailed analysis of protein topology of extracellular vesicles‐evidence of unconventional membrane protein orientation, Sci Rep, 6, 36338, 10.1038/srep36338

10.1182/blood-2007-03-078709

10.1007/978-1-60327-412-8_20

10.1080/19336918.2016.1273307

10.1039/C5OB01451D

10.1074/jbc.M109.041152

10.1155/2014/619829

10.1073/pnas.1304266110

10.3402/jev.v3.24641

10.1371/journal.pone.0049723

10.1007/s00018-014-1618-z

10.1038/srep33641

Paolini L, 2016, Residual matrix from different separation techniques impacts exosome biological activity, Sci Rep, 6, 23550, 10.1038/srep23550

10.1182/blood-2010-09-307595

10.1038/s41598-017-15717-7

10.1126/science.1153124

10.1371/journal.pone.0124481

10.1523/JNEUROSCI.1429-16.2016

10.5966/sctm.2014-0280

10.1038/ncomms13588

Savina A, 2002, The exosome pathway in K562 cells is regulated by Rab11, J Cell Sci, 115, 2505, 10.1242/jcs.115.12.2505

10.1038/ncb2000

10.1083/jcb.200911018

10.1083/jcb.201504136

10.1038/ncb2574

10.1073/pnas.1713433114

10.1083/jcb.201601025

10.1016/j.bpj.2017.05.032

Chalmin F, 2010, Membrane‐associated Hsp72 from tumor‐derived exosomes mediates STAT3‐dependent immunosuppressive function of mouse and human myeloid‐derived suppressor cells, J Clin Invest, 120, 457

10.1182/blood-2011-02-338004

10.1074/jbc.M301642200

10.1080/15548627.2017.1395992

10.7554/eLife.17180

Atai NA, 2013, Heparin blocks transfer of extracellular vesicles between donor and recipient cells, J Neurooncol

10.1038/s41467-017-00767-2

10.1073/pnas.1200448109

10.1016/j.cub.2009.09.059

10.1161/ATVBAHA.110.222703

10.1097/TA.0b013e318265d04b

Yu X, 2018, Bubbles induce endothelial microparticle formation via a calcium‐dependent pathway involving flippase inactivation and rho kinase activation, Cell Physiol Biochem, 46, 965, 10.1159/000488825

10.1158/0008-5472.CAN-08-3860

10.1038/nrmicro3525

10.1146/annurev-cellbio-101512-122326

10.1016/j.febslet.2013.03.012

10.1083/jcb.200508014

10.1016/j.bbagen.2011.05.003

10.1080/20013078.2017.1378056

Bobrie A, 2012, Diverse subpopulations of vesicles secreted by different intracellular mechanisms are present in exosome preparations obtained by differential ultracentrifugation, J Extracell Vesicles, 1, 18297, 10.3402/jev.v1i0.18397

10.1038/nm.2753

10.3402/jev.v2i0.20384

10.1093/bioinformatics/btu741

10.1371/journal.pbio.1001450

10.1002/pmic.200900351

10.3402/jev.v4.27497