Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year‐on‐year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non‐vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its ‘Minimal Information for Studies of Extracellular Vesicles’, which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly.

Related collections

Most cited references 527

Record: found
Abstract: found
Article: found

Is Open Access

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 Théry, Kenneth W Witwer, Elena Aikawa … (2019)

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.

0 comments Cited 3543 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: found

Is Open Access

NIA-AA Research Framework: Toward a biological definition of Alzheimer’s disease

Clifford R. Jack, David Bennett, Kaj Blennow … (2018)

In 2011, the National Institute on Aging and Alzheimer’s Association created separate diagnostic recommendations for the preclinical, mild cognitive impairment, and dementia stages of Alzheimer’s disease. Scientific progress in the interim led to an initiative by the National Institute on Aging and Alzheimer’s Association to update and unify the 2011 guidelines. This unifying update is labeled a “research framework” because its intended use is for observational and interventional research, not routine clinical care. In the National Institute on Aging and Alzheimer’s Association Research Framework, Alzheimer’s disease (AD) is defined by its underlying pathologic processes that can be documented by postmortem examination or in vivo by biomarkers. The diagnosis is not based on the clinical consequences of the disease (i.e., symptoms/signs) in this research framework, which shifts the definition of AD in living people from a syndromal to a biological construct. The research framework focuses on the diagnosis of AD with biomarkers in living persons. Biomarkers are grouped into those of β amyloid deposition, pathologic tau, and neurodegeneration [AT(N)]. This ATN classification system groups different biomarkers (imaging and biofluids) by the pathologic process each measures. The AT(N) system is flexible in that new biomarkers can be added to the three existing AT(N) groups, and new biomarker groups beyond AT(N) can be added when they become available. We focus on AD as a continuum, and cognitive staging may be accomplished using continuous measures. However, we also outline two different categorical cognitive schemes for staging the severity of cognitive impairment: a scheme using three traditional syndromal categories and a six-stage numeric scheme. It is important to stress that this framework seeks to create a common language with which investigators can generate and test hypotheses about the interactions among different pathologic processes (denoted by biomarkers) and cognitive symptoms. We appreciate the concern that this biomarker-based research framework has the potential to be misused. Therefore, we emphasize, first, it is premature and inappropriate to use this research framework in general medical practice. Second, this research framework should not be used to restrict alternative approaches to hypothesis testing that do not use biomarkers. There will be situations where biomarkers are not available or requiring them would be counterproductive to the specific research goals (discussed in more detail later in the document). Thus, biomarker-based research should not be considered a template for all research into age-related cognitive impairment and dementia; rather, it should be applied when it is fit for the purpose of the specific research goals of a study. Importantly, this framework should be examined in diverse populations. Although it is possible that β-amyloid plaques and neurofibrillary tau deposits are not causal in AD pathogenesis, it is these abnormal protein deposits that define AD as a unique neurodegenerative disease among different disorders that can lead to dementia. We envision that defining AD as a biological construct will enable a more accurate characterization and understanding of the sequence of events that lead to cognitive impairment that is associated with AD, as well as the multifactorial etiology of dementia. This approach also will enable a more precise approach to interventional trials where specific pathways can be targeted in the disease process and in the appropriate people.

0 comments Cited 2748 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments.

Stephen A. Bustin, Vladimir Benes, Jeremy A. Garson … (2009)

Currently, a lack of consensus exists on how best to perform and interpret quantitative real-time PCR (qPCR) experiments. The problem is exacerbated by a lack of sufficient experimental detail in many publications, which impedes a reader's ability to evaluate critically the quality of the results presented or to repeat the experiments. The Minimum Information for Publication of Quantitative Real-Time PCR Experiments (MIQE) guidelines target the reliability of results to help ensure the integrity of the scientific literature, promote consistency between laboratories, and increase experimental transparency. MIQE is a set of guidelines that describe the minimum information necessary for evaluating qPCR experiments. Included is a checklist to accompany the initial submission of a manuscript to the publisher. By providing all relevant experimental conditions and assay characteristics, reviewers can assess the validity of the protocols used. Full disclosure of all reagents, sequences, and analysis methods is necessary to enable other investigators to reproduce results. MIQE details should be published either in abbreviated form or as an online supplement. Following these guidelines will encourage better experimental practice, allowing more reliable and unequivocal interpretation of qPCR results.

0 comments Cited 1864 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Joshua A. Welsh:

ORCID: https://orcid.org/0000-0002-1097-9756

joadwe@outlook.com

Deborah C. I. Goberdhan:

ORCID: https://orcid.org/0000-0003-0645-6714

deborah.goberdhan@wrh.ox.ac.uk

Lorraine O'Driscoll: lodrisc@tcd.ie

Clotilde Théry:

ORCID: https://orcid.org/0000-0001-8294-6884

Clotilde.Thery@curie.fr

Kenneth W. Witwer:

ORCID: https://orcid.org/0000-0003-1664-4233

kwitwer1@jhmi.edu

Journal

Journal ID (nlm-ta): J Extracell Vesicles

Journal ID (iso-abbrev): J Extracell Vesicles

Journal ID (doi): 10.1002/(ISSN)2001-3078

Journal ID (publisher-id): JEV2

Title: Journal of Extracellular Vesicles

Publisher: John Wiley and Sons Inc. (Hoboken )

ISSN (Electronic): 2001-3078

Publication date (Electronic): 07 February 2024

Publication date (Print): February 2024

Volume: 13

Issue: 2 ( doiID: 10.1002/jev2.v13.2 )

Electronic Location Identifier: e12404

Affiliations

[ ¹ ] Translational Nanobiology Section, Laboratory of Pathology National Cancer Institute, National Institutes of Health Bethesda Maryland USA

[ ² ] Nuffield Department of Women's and Reproductive Health University of Oxford, Women's Centre, John Radcliffe Hospital Oxford UK

[ ³ ] School of Pharmacy and Pharmaceutical Sciences Trinity College Dublin Dublin Ireland

[ ⁴ ] Trinity Biomedical Sciences Institute Trinity College Dublin Dublin Ireland

[ ⁵ ] Trinity St. James's Cancer Institute Trinity College Dublin Dublin Ireland

[ ⁶ ] Department of Genetics, Cell‐ and Immunobiology Semmelweis University Budapest Hungary

[ ⁷ ] HCEMM‐SU Extracellular Vesicle Research Group Semmelweis University Budapest Hungary

[ ⁸ ] HUN‐REN‐SU Translational Extracellular Vesicle Research Group Semmelweis University Budapest Hungary

[ ⁹ ] Faculty of Medical and Health Sciences The University of Auckland Auckland New Zealand

[ ¹⁰ ] Department of Molecular Biotechnology and Health Sciences University of Turin Turin Italy

[ ¹¹ ] University of Georgia Athens Georgia USA

[ ¹² ] Department of Surgery, Division of Cancer Biology and Therapeutics Cedars‐Sinai Medical Center Los Angeles California USA

[ ¹³ ] Department CDL Research University Medical Center Utrecht Utrecht The Netherlands

[ ¹⁴ ] University of Virginia Health System Charlottesville Virginia USA

[ ¹⁵ ] Exosomes Laboratory, Center for Cooperative Research in Biosciences Basque Research and Technology Alliance Derio Spain

[ ¹⁶ ] Metabolomics Platform, Center for Cooperative Research in Biosciences Basque Research and Technology Alliance Derio Spain

[ ¹⁷ ] IKERBASQUE, Basque Foundation for Science Bilbao Spain

[ ¹⁸ ] Otorhinolaryngology Hospital, The First Affiliated Hospital Sun Yat‐sen University Guangzhou China

[ ¹⁹ ] Extracellular Vesicle Research and Clinical Translational Center The First Affiliated Hospital, Sun Yat‐sen University Guangzhou China

[ ²⁰ ] Institute for Health and Sport Victoria University Melbourne Australia

[ ²¹ ] Faculty of Medicine University of Ljubljana Ljubljana Slovenia

[ ²² ] Institute of Molecular and Cell Biology (IMCB) Agency for Science, Technology and Research (A*STAR) Singapore Singapore

[ ²³ ] Paracrine Therapeutics Pte. Ltd. Singapore Singapore

[ ²⁴ ] Department of Surgery, YLL School of Medicine National University Singapore Singapore Singapore

[ ²⁵ ] Thomas Jefferson University Philadelphia Pennsylvania USA

[ ²⁶ ] Stem Cell Facility All India Institute of Medical Sciences New Delhi India

[ ²⁷ ] Chinese University of Hong Kong Hong Kong Hong Kong S.A.R.

[ ²⁸ ] QIMR Berghofer Medical Research Institute Brisbane Australia

[ ²⁹ ] Laboratory of Experimental Clinical Chemistry, Amsterdam University Medical Centers, Location AMC University of Amsterdam Amsterdam The Netherlands

[ ³⁰ ] Amsterdam Vesicle Center, Amsterdam University Medical Centers, Location AMC University of Amsterdam Amsterdam The Netherlands

[ ³¹ ] Tokyo Medical University Tokyo Japan

[ ³² ] Icahn School of Medicine at Mount Sinai New York New York USA

[ ³³ ] Laboratório de Imunologia Celular e Bioquímica de Fungos e Protozoários, Departamento de Ciências Farmacêuticas, Instituto de Ciências Ambientais, Químicas e Farmacêuticas Universidade Federal de São Paulo (UNIFESP) Campus Diadema Diadema Brazil

[ ³⁴ ] Department of Laboratory Medicine, Nanfang Hospital Southern Medical University Guangzhou China

[ ³⁵ ] Department of Pathology Vanderbilt University Medical Center Nashville Tennessee USA

[ ³⁶ ] Genentech South San Francisco California USA

[ ³⁷ ] Department of Molecular Medicine, Beckman Research Institute City of Hope Comprehensive Cancer Center Duarte California USA

[ ³⁸ ] Department of Molecular and Translational Medicine University of Brescia Brescia Italy

[ ³⁹ ] Center for Colloid and Surface Science (CSGI) Florence Italy

[ ⁴⁰ ] National Center for Gene Therapy and Drugs based on RNA Technology Padua Italy

[ ⁴¹ ] Weatherall Institute of Molecular Medicine University of Oxford Oxford UK

[ ⁴² ] Consiglio Nazionale delle Ricerche ‐ Istituto per lo Studio dei Materiali Nanostrutturati Bologna Italy

[ ⁴³ ] Consorzio Interuniversitario per lo Sviluppo dei Sistemi a Grande Interfase Florence Italy

[ ⁴⁴ ] Kidney Research Centre Ottawa Hopsital Research Institute Ottawa Canada

[ ⁴⁵ ] Department of Cellular and Molecular Medicine University of Ottawa Ottawa Canada

[ ⁴⁶ ] School of Pharmaceutical Sciences University of Ottawa Ottawa Canada

[ ⁴⁷ ] Department of Biomedical Engineering University of California Davis California USA

[ ⁴⁸ ] Division of Pharmaceutics and Pharmacology, College of Pharmacy The Ohio State University Columbus Ohio USA

[ ⁴⁹ ] Comprehensive Cancer Center The Ohio State University Columbus Ohio USA

[ ⁵⁰ ] Sahlgrenska Center for Cancer Research, Department of Surgery, Institute of Clinical Sciences Sahlgrenska Academy, University of Gothenburg Gothenburg Sweden

[ ⁵¹ ] Wallenberg Centre for Molecular and Translational Medicine, Institute of Clinical Sciences Sahlgrenska Academy, University of Gothenburg Gothenburg Sweden

[ ⁵² ] Department of Biomedicine University Hospital Basel Basel Switzerland

[ ⁵³ ] Department of Biomedicine University of Basel Basel Switzerland

[ ⁵⁴ ] Department of Oncology University of Oxford Oxford UK

[ ⁵⁵ ] Departments of Neurology and Psychiatry Johns Hopkins University School of Medicine Baltimore Maryland USA

[ ⁵⁶ ] Laboratory of Experimental Cancer Research, Department of Human Structure and Repair Ghent University Ghent Belgium

[ ⁵⁷ ] Cancer Research Institute Ghent Ghent Belgium

[ ⁵⁸ ] Barnett Institute of Chemical and Biological Analysis, Department of Chemistry and Chemical Biology Northeastern University Boston Massachusetts USA

[ ⁵⁹ ] Department of Cancer Biology and Molecular Medicine, Beckman Research Institute City of Hope Comprehensive Cancer Center Duarte California USA

[ ⁶⁰ ] Bio‐pharmaceutical Manufacturing and Academic Resource Center (BioMARC) Infectious Disease Research Center, Colorado State University Fort Collins Colorado USA

[ ⁶¹ ] Department of Rheumatology University Hospital Basel Basel Switzerland

[ ⁶² ] Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition Institute of Medicine at Sahlgrenska Academy, University of Gothenburg Gothenburg Sweden

[ ⁶³ ] Krefting Research Centre, Institute of Medicine at Sahlgrenska Academy University of Gothenburg Gothenburg Sweden

[ ⁶⁴ ] Erasmus MC Cancer Institute University Medical Center Rotterdam, Department of Urology Rotterdam The Netherlands

[ ⁶⁵ ] College of Medicine and Public Health Flinders University Adelaide Australia

[ ⁶⁶ ] Department of Physics and Astronomy, and LaserLaB Amsterdam Vrije Universiteit Amsterdam Amsterdam The Netherlands

[ ⁶⁷ ] Department of Transfusion Medicine, University Hospital Salzburger Landeskliniken GmbH of Paracelsus Medical University Salzburg Austria

[ ⁶⁸ ] GMP Unit, Paracelsus Medical University Salzburg Austria

[ ⁶⁹ ] Transfer Centre for Extracellular Vesicle Theralytic Technologies, EV‐TT Salzburg Austria

[ ⁷⁰ ] Expansion Therapeutics, Structural Biology and Biophysics Jupiter Florida USA

[ ⁷¹ ] Department of Anesthesiology & Perioperative Medicine Oregon Health & Science University Portland Oregon USA

[ ⁷² ] Department of Stem Cells and Developmental Biology, Cell Science Research Center Royan Institute for Stem Cell Biology and Technology, ACECR Tehran Iran

[ ⁷³ ] Celer Diagnostics Toronto Canada

[ ⁷⁴ ] Waipapa Taumata Rau University of Auckland Auckland New Zealand

[ ⁷⁵ ] Wyss Institute for Biologically Inspired Engineering Harvard University Boston Massachusetts USA

[ ⁷⁶ ] Universidad de la República Montevideo Uruguay

[ ⁷⁷ ] Institut Pasteur de Montevideo Montevideo Uruguay

[ ⁷⁸ ] Biological Nanochemistry Research Group Institute of Materials and Environmental Chemistry, Research Centre for Natural Sciences Budapest Hungary

[ ⁷⁹ ] Department of Biophysics and Radiation Biology Semmelweis University Budapest Hungary

[ ⁸⁰ ] Biomedical Engineering and Physics, Amsterdam UMC, location AMC University of Amsterdam Amsterdam The Netherlands

[ ⁸¹ ] Laboratory of Experimental Clinical Chemistry, Amsterdam UMC, location AMC University of Amsterdam Amsterdam The Netherlands

[ ⁸² ] Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine Utrecht University Utrecht The Netherlands

[ ⁸³ ] University of Denver Denver USA

[ ⁸⁴ ] International Society for Extracellular Vesicles

[ ⁸⁵ ] Institut Curie, INSERM U932 PSL University Paris France

[ ⁸⁶ ] CurieCoreTech Extracellular Vesicles, Institut Curie Paris France

[ ⁸⁷ ] Department of Molecular and Comparative Pathobiology Johns Hopkins University School of Medicine Baltimore Maryland USA

[ ⁸⁸ ] EV Core Facility “EXCEL”, Institute for Basic Biomedical Sciences Johns Hopkins University School of Medicine Baltimore Maryland USA

[ ⁸⁹ ] The Richman Family Precision Medicine Center of Excellence in Alzheimer's Disease Johns Hopkins University School of Medicine Baltimore Maryland USA

Author notes

[*] [* ] Correspondence

Joshua Welsh, Email: joadwe@ 123456outlook.com ; Deborah C. I. Goberdhan, Email: deborah.goberdhan@ 123456wrh.ox.ac.uk ; Lorraine O'Driscoll, Email: lodrisc@ 123456tcd.ie ; Clotilde Théry, Email: Clotilde.Thery@ 123456curie.fr ; Kenneth W. Witwer, Email: kwitwer1@ 123456jhmi.edu

[†]

MISEV Organizing Committee.

[‡]

ISEV Board 2020‐2022.

[§]

ISEV Board 2022‐2024.

[∥]

Original section drafting contribution.

Author information

Joshua A. Welsh https://orcid.org/0000-0002-1097-9756

Deborah C. I. Goberdhan https://orcid.org/0000-0003-0645-6714

Edit I. Buzas https://orcid.org/0000-0002-3744-206X

Benedetta Bussolati https://orcid.org/0000-0002-3663-5134

Houjian Cai https://orcid.org/0000-0003-4887-2652

Juan M. Falcon‐Perez https://orcid.org/0000-0003-3133-0670

Andrew F. Hill https://orcid.org/0000-0001-5581-2354

Metka Lenassi https://orcid.org/0000-0002-9488-6855

Sujata Mohanty https://orcid.org/0000-0002-0047-4914

Rienk Nieuwland https://orcid.org/0000-0002-5671-3400

Takahiro Ochiya https://orcid.org/0000-0002-0776-9918

Susmita Sahoo https://orcid.org/0000-0002-7279-1564

Ana C. Torrecilhas https://orcid.org/0000-0001-5724-2199

Lei Zheng https://orcid.org/0000-0003-2576-8780

Andries Zijlstra https://orcid.org/0000-0001-8460-8803

Marco Brucale https://orcid.org/0000-0001-7244-4389

Randy P. Carney https://orcid.org/0000-0001-8193-1664

Rossella Crescitelli https://orcid.org/0000-0002-1714-3169

Norman J. Haughey https://orcid.org/0000-0001-5194-4122

Elena S. Martens‐Uzunova https://orcid.org/0000-0002-5363-2525

Lauren A. Newman https://orcid.org/0000-0003-3303-1666

Eva Rohde https://orcid.org/0000-0001-8692-886X

Ursula S. Sandau https://orcid.org/0000-0002-3646-7089

Julie A. Saugstad https://orcid.org/0000-0002-2996-9611

Faezeh Shekari https://orcid.org/0000-0001-6026-5412

Juan P. Tosar https://orcid.org/0000-0002-2021-2479

Marca H. M. Wauben https://orcid.org/0000-0003-0360-0311

Ann M. Wehman https://orcid.org/0000-0001-9826-4132

Alan J. Zimmerman https://orcid.org/0000-0001-6280-4790

Clotilde Théry https://orcid.org/0000-0001-8294-6884

Kenneth W. Witwer https://orcid.org/0000-0003-1664-4233

Article

Publisher ID: JEV212404

DOI: 10.1002/jev2.12404

PMC ID: 10850029

PubMed ID: 38326288

SO-VID: c09d8d75-6177-4b90-b7ac-b88006b4d6ad

License:

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

History

Date revision received : 15 December 2023

Date received : 15 December 2023

Date accepted : 19 December 2023

Page count

Figures: 2, Tables: 4, Pages: 84, Words: 70460

Custom metadata

source-schema-version-number 2.0

cover-date February 2024

details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_JATSPMC version:6.3.6 mode:remove_FC converted:07.02.2024

Keywords: ectosomes,exosomes,extracellular vesicles,extracellular particles,guidelines,microparticles,microvesicles,minimal information requirements,misev,reproducibility,rigor,standardisation

Data availability:

Keywords: ectosomes, exosomes, extracellular vesicles, extracellular particles, guidelines, microparticles, microvesicles, minimal information requirements, misev, reproducibility, rigor, standardisation

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Read this article at

Abstract

Related collections

Bacterial extracellular vesicles

Most cited references 527

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

NIA-AA Research Framework: Toward a biological definition of Alzheimer’s disease

The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments.

Author and article information

Contributors

Journal

Affiliations

Author notes

Author information

Article

History

Page count

Categories

Custom metadata

Comments

Comment on this article

Similar content 228

Cited by 73

Most referenced authors 10,232