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

Clotilde Thery (1) , Kenneth Witwer (2) , Elena Aikawa , Maria Jose Alcaraz , Johnathon Anderson , Ramaroson Andriantsitohaina (3) , Anna Antoniou , Tanina Arab (4) , Fabienne Archer (5) , Georgia Atkin-Smith , D Craig Ayre , Jean-Marie Bach (6) , Daniel Bachurski , Hossein Baharvand , Leonora Balaj , Shawn Baldacchino , Natalie Bauer , Amy Baxter , Mary Bebawy , Carla Beckham , Apolonija Bedina Zavec (7) , Abderrahim Benmoussa (8) , Anna Maria Berardi , Paolo Bergese , Ewa Bielska , Cherie Blenkiron , Sylwia Bobis-Wozowicz , Eric Boilard (9) , Wilfrid Boireau (10) , Antonella Bongiovanni , Francesc Borràs , Steffi Bosch (6) , Chantal M. Boulanger (11) , Xandra Breakefield , Andrew Breglio , Meadhbh A Brennan (12) , David Brigstock , Alain Brisson (13) , Marike Ld Broekman , Jacqueline Bromberg , Paulina Bryl-Górecka , Shilpa Buch , Amy Buck , Dylan Burger , Sara Busatto , Dominik Buschmann , Benedetta Bussolati (14) , Edit Buzás , James Bryan Byrd , Giovanni Camussi (15) , David Rf Carter , Sarah Caruso , Lawrence Chamley , Yu-Ting Chang , Chihchen Chen , Shuai Chen , Lesley Cheng (16) , Andrew Chin (17) , Aled Clayton (18) , Stefano Clerici , Alex Cocks , Emanuele Cocucci , Robert Coffey , Anabela Cordeiro-Da-Silva (19) , Yvonne Couch , Frank Aw Coumans , Beth Coyle , Rossella Crescitelli , Miria Ferreira Criado , Crislyn D’souza-Schorey , Saumya Das , Amrita Datta Chaudhuri , Paola de Candia , Eliezer de Santana , Olivier de Wever (20) , Hernando del Portillo , Tanguy Demaret , Sarah Deville , Andrew Devitt , Bert Dhondt (20) , Dolores Di Vizio , Lothar Dieterich , Vincenza Dolo , Ana Paula Dominguez Rubio , Massimo Dominici (21) , Mauricio Dourado , Tom Ap Driedonks , Filipe Duarte , Heather Duncan , Ramon Eichenberger , Karin Ekström , Samir El Andaloussi (22) , Céline Elie-Caille (10) , Uta Erdbrügger , Juan Falcón-Pérez (23) , Farah Fatima , Jason Fish , Miguel Flores-Bellver , András Försönits , Annie Frelet-Barrand (10) , Fabia Fricke , Gregor Fuhrmann , Susanne Gabrielsson , Ana Gámez-Valero , Chris Gardiner , Kathrin Gartner (24) , Raphael Gaudin , Yong Song Gho , Bernd Giebel (25) , Caroline Gilbert (26) , Mario Gimona , Ilaria Giusti , Deborah Ci Goberdhan , André Görgens , Sharon Gorski , David Greening , Julia Christina Gross , Alice Gualerzi , Gopal Gupta , Dakota Gustafson , Aase Handberg , Reka Haraszti , Paul Harrison (27) , Hargita Hegyesi , An Hendrix (20) , Andrew Hill , Fred Hochberg , Karl F Hoffmann (28) , Beth Holder , Harry Holthöfer (29) , Baharak Hosseinkhani , Guoku Hu , Yiyao Huang , Veronica Huber , Stuart Hunt , Ahmed Gamal-Eldin Ibrahim , Tsuneya Ikezu , Jameel Inal , Mustafa Isin , Alena Ivanova , Hannah Jackson , Soren Jacobsen (30) , Steven Jay , Muthuvel Jayachandran , Guido Jenster , Lanzhou Jiang , Suzanne Johnson , Jennifer Jones (31) , Ambrose Jong , Tijana Jovanovic-Talisman , Stephanie Jung , Raghu Kalluri , Shin-Ichi Kano , Sukhbir Kaur , Yumi Kawamura , Evan Keller , Delaram Khamari , Elena Khomyakova , Anastasia Khvorova , Peter Kierulf , Kwang Pyo Kim , Thomas Kislinger , Mikael Klingeborn , David Klinke , Miroslaw Kornek , Maja Kosanović , Árpád Ferenc Kovács , Eva-Maria Krämer-Albers (32) , Susanne Krasemann , Mirja Krause , Igor Kurochkin , Gina Kusuma , Sören Kuypers , Saara Laitinen , Scott Langevin , Lucia Languino , Joanne Lannigan , Cecilia Lässer , Louise Laurent , Grégory Lavieu (33) , Elisa Lázaro-Ibáñez , Soazig Le Lay (3) , Myung-Shin Lee , Yi Xin Fiona Lee , Debora Lemos , Metka Lenassi , Aleksandra Leszczynska , Isaac Ts Li , Ke Liao , Sten Libregts , Erzsebet Ligeti , Rebecca Lim , Sai Kiang Lim , Aija Linē , Karen Linnemannstöns , Alicia Llorente , Catherine Lombard , Magdalena Lorenowicz , Ákos Lörincz , Jan Lötvall (34) , Jason Lovett , Michelle Lowry , Xavier Loyer (11) , Quan Lu , Barbara Lukomska , Taral Lunavat , Sybren Ln Maas , Harmeet Malhi , Antonio Marcilla (35) , Jacopo Mariani , Javier Mariscal , Elena Martens-Uzunova , Lorena Martin-Jaular , M Carmen Martinez (3) , Vilma Regina Martins , Mathilde Mathieu (36) , Suresh Mathivanan (16) , Marco Maugeri , Lynda Mcginnis , Mark Mcvey , David Meckes , Katie Meehan , Inge Mertens (37) , Valentina Minciacchi , Andreas Möller , Malene Møller Jørgensen , Aizea Morales-Kastresana , Jess Morhayim , François Mullier (38) , Maurizio Muraca (39) , Luca Musante , Veronika Mussack , Dillon Muth , Kathryn Myburgh , Tanbir Najrana , Muhammad Nawaz , Irina Nazarenko , Peter Nejsum (40) , Christian Neri (41) , Tommaso Neri , Rienk Nieuwland , Leonardo Nimrichter , John Nolan (42) , Esther Nm Nolte-’t Hoen , Nicole Noren Hooten , Lorraine O’driscoll , Tina O’grady , Ana O’loghlen , Takahiro Ochiya , Martin Olivier (43) , Alberto Ortiz (44) , Luis Ortiz (45) , Xabier Osteikoetxea , Ole Østergaard , Matias Ostrowski , Jaesung Park , D. Michiel Pegtel , Héctor Peinado (46) , Francesca Perut (47) , Michael Pfaffl , Donald G. Phinney (48) , Bartijn Ch Pieters , Ryan Pink , David Pisetsky , Elke Pogge von Strandmann , Iva Polakovicova , Ivan Kh Poon , Bonita Powell , Ilaria Prada , Lynn Pulliam , Peter Quesenberry , Annalisa Radeghieri , Robert Raffai , Stefania Raimondo (49) , Janusz Rak (50) , Marcel Ramirez , Graça Raposo (51) , Morsi Rayyan , Neta Regev-Rudzki , Franz Ricklefs , Paul Robbins , David Roberts (52) , Silvia Rodrigues , Eva Rohde , Sophie Rome (53) , Kasper Ma Rouschop , Aurelia Rughetti , Ashley Russell , Paula Saá , Susmita Sahoo (54) , Edison Salas-Huenuleo , Catherine Sánchez , Julie Saugstad , Meike Saul , Raymond Schiffelers (55) , Raphael Schneider (56) , Tine Hiorth Schøyen , Aaron Scott , Eriomina Shahaj , Shivani Sharma , Olga Shatnyeva , Faezeh Shekari , Ganesh Vilas Shelke , Ashok Shetty , Kiyotaka Shiba , Pia R-M Siljander , Andreia Silva , Agata Skowronek , Orman Snyder , Rodrigo Pedro Soares (57) , Barbara Sódar , Carolina Soekmadji , Javier Sotillo , Philip Stahl , Willem Stoorvogel , Shannon Stott , Erwin Strasser , Simon Swift , Hidetoshi Tahara , Muneesh Tewari , Kate Timms , Swasti Tiwari , Rochelle Tixeira , Mercedes Tkach , Wei Seong Toh , Richard Tomasini (58) , Ana Cláudia Torrecilhas (59) , Juan Pablo Tosar (60) , Vasilis Toxavidis , Lorena Urbanelli (61) , Pieter Vader , Bas Wm van Balkom , Susanne van Der Grein (62) , Jan van Deun (20) , Martijn Jc van Herwijnen , Kendall van Keuren-Jensen , Guillaume van Niel (63) , Martin van Royen , Andre van Wijnen , M Helena Vasconcelos , Ivan Vechetti , Tiago Veit , Laura Vella , Emilie Velot (64) , Frederik Verweij (63) , Beate Vestad , Jose Viñas , Tamás Visnovitz , Krisztina Vukman , Jessica Wahlgren , Dionysios Watson , Marca Hm Wauben , Alissa Weaver , Jason Webber , Viktoria Weber , Ann M. Wehman (65) , Daniel Weiss (66) , Joshua Welsh , Sebastian Wendt , Asa Wheelock , Zoltán Wiener , Leonie Witte , Joy Wolfram , Angeliki Xagorari , Patricia Xander , Jing Xu (67) , Xiaomei Yan (68) , María Yáñez-Mó , Hang Yin (69) , Yuana Yuana , Valentina Zappulli , Jana Zarubova , Vytautas Žėkas , Jian-Ye Zhang , Zezhou Zhao , Lei Zheng , Alexander Zheutlin , Antje Zickler (70) , Pascale Zimmermann (58) , Angela Zivkovic , Davide Zocco , Ewa Zuba-Surma

1 Immunité et cancer
2 Johns Hopkins University School of Medicine [Baltimore]
3 SOPAM - Stress Oxydant et Pathologies Métaboliques
4 PRISM - Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192
5 IVPC - Infections Virales et Pathologie Comparée - UMR 754
6 IECM - Immuno-Endocrinologie Cellulaire et Moléculaire
7 Department for Molecular Biology and Nanobiotechnology
8 BIOTARGEN - Biologie, génétique et thérapies ostéoarticulaires et respiratoires
9 IPMC - Institut de pharmacologie moléculaire et cellulaire
10 FEMTO-ST - Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174)
11 PARCC - UMR-S U970 - Paris-Centre de Recherche Cardiovasculaire
12 PhAN - Physiopathologie des Adaptations Nutritionnelles
13 IECB - Imagerie Moléculaire et Nanobiotechnologies - Institut Européen de Chimie et Biologie
14 Molecular Biotechnology Center
15 UNITO - Università degli studi di Torino = University of Turin
16 Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science
17 Centre for Sustainable Tropical Fisheries and Aquaculture
18 Department of Oncology - Pathology
19 Departamento de Ciências Biológicas
20 Laboratory of Experimental Cancer Research, Department of Radiation Oncology and Experimental Cancer Research, Cancer Research Institute Ghent (CRIG)
21 Laboratory of Cellular Therapy - Department of Medical and Surgical Sciences for Children and Adults [Modena, Italy]
22 Clinical Research Center, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Huddinge, Sweden
23 CIC bioGUNE - Center for Cooperative Research in Biosciences = Centro de Investigación cooperativa en biociencia (Derio, Biscay, Espagne)
24 Partner site Munich
25 Institute for Transfusion Medicine
26 MECADEV - Mécanismes Adaptatifs et Evolution
27 Psychiatry
28 IBERS - Institute of Biological, Environmental and Rural Sciences
29 Department of Bacteriology and Immunology [Helsinki]
30 Rigshospitalet [Copenhagen]
31 Dalhousie University [Halifax]
32 Department of Biology, Molecular Cell Biology, University of Mainz
33 Glycobiologie et signalisation cellulaire
34 Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition
35 Universidad de Alicante
36 UPEC ESPE Créteil - École supérieure du professorat et de l'éducation - Académie de Créteil
37 UA - University of Antwerp
38 UCL - Université Catholique de Louvain = Catholic University of Louvain
39 Research Institute
40 Department of Veterinary Disease Biology [Copenhagen]
41 Brain-C - Biologie et Pathologie du Neurone
42 Department of Mathematics and Statistics
43 University of Pretoria [South Africa]
44 EIVP - Ecole des Ingénieurs de la Ville de Paris
45 UPF - Universitat Pompeu Fabra [Barcelona]
46 Instituto de Investigaciones Biomedicas
47 Istituto Ortopedico Rizzoli
48 Department of Molecular Therapeutics
49 LIG - Laboratoire d'Informatique de Grenoble
50 Montreal Children's Hospital
51 CDC - Compartimentation et dynamique cellulaires
52 NCI-NIH - National Cancer Institute [Bethesda]
53 CarMeN - Cardiovasculaire, métabolisme, diabétologie et nutrition
54 Cardiovascular Research Center
55 University Medical Center [Utrecht]
56 University of Toronto
57 Fiocruz Minas - René Rachou Research Center / Instituto René Rachou [Belo Horizonte, Brésil]
58 CRCM - Centre de Recherche en Cancérologie de Marseille
59 Unifesp - Federal University of Sao Paulo
60 Functional Genomics / Genómica Funcional [Montevideo]
61 Dipartimento di Medicina Sperimentale e Scienze Biochimiche
62 Instituto de Investigacion Sanitaria del Hospital de la Princesa
63 CDC - Compartimentation et dynamique cellulaires
64 IMoPA - Ingénierie Moléculaire et Physiopathologie Articulaire
65 Department of Physiology
66 University of Vermont [Burlington]
67 Peking University [Beijing]
68 SDAU - Shandong Agricultural University
69 Institute of Chinese Medical Sciences - State Key Laboratory of Quality Research in Chinese Medicine Taipa, Macau SAR,
70 Human Genetics

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.

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

Domains: Life Sciences [q-bio]; Cellular Biology

Clotilde Thery, Kenneth Witwer, Elena Aikawa, Maria Jose Alcaraz, Johnathon Anderson, et al.. 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, 2018, 7 (1), pp.1535750. ⟨10.1080/20013078.2018.1535750⟩. ⟨hal-02323217⟩