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Cited by 11,099Extracellular vesicles in diseaseCellular transport and secretionCaveolin-1 and cellular processes

Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

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Théry, Clotilde, Witwer, Kenneth W, Aikawa, Elena, Alcaraz, Maria Jose, Anderson, Johnathon D, Andriantsitohaina, Ramaroson, Antoniou, Anna, Arab, Tanina +374 more·2018·Journal of Extracellular Vesicles
DOI 10.1080/20013078.2018.1535750PMC PMC6322352
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Abstract

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

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  • The establishment of minimum-information guidelines such as MIAME and MISEV improved the quality, harmonization, and reproducibility of data reporting.

    “The establishment of the so-called “minimum information for experimentation” (for example, “Minimum information about a microarray experiment” (MIAME) or “Minimal information for studies of extracellular vesicles” (MISEV)) led to an improvement in data reporting quality, harmonization, and reproducibility2,3.”

    From Guidelines for minimal information on cellular senescence experimentation in vivo (2024) · cites this paper as [2]

    The Introduction identifies MISEV as minimum-information guidelines intended to improve EV reporting, reliability, and reproducibility. But it says the MISEV2014 authors *hoped* to improve reliability and reproducibility; it does not establish that the guidelines led to the claimed improvements in reporting quality, harmonization, and reproducibility. This source concerns MISEV, while the sentence also cites another source for MIAME. (LLM, conf=0.85)

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  • MISEV2018 has advised the use of "operational terms" to name isolated EVs with descriptions of isolation method, such as distinct sizes (sEVs <200 nm, m/lEVs >200 nm), specific proteins/cargos/compositions and cellular origins.

    “In such instances, MISEV2018 has advised the use of “operational terms” to name the isolated EVs with descriptions of isolation method, such as distinct sizes (small EVs (sEVs), less than 200 nm), medium and large EVs (m/lEVs, larger than 200 nm)), specific proteins/cargos/compositions and cellular origins [125].”

    From Extracellular vesicles as nanotheranostic platforms for targeted neurological disorder interventions (2024) · cites this paper as [125]

    The Nomenclature section recommends operational terms based on EV size, biochemical composition, and conditions or cell of origin, including the stated sEV and m/lEV size examples. The Conclusions separately require detailed reporting of separation or isolation procedures; they do not present the isolation method as one of the operational naming categories. (LLM, conf=0.84)

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  • Large extracellular vesicles are generated by direct outward budding of the plasma membrane, producing microvesicles, microparticles and large vesicles ranging from ∼100 nm to 1 μm in diameter.

    “In contrast, large extracellular vesicles are generated by direct outward budding of the plasma membrane, producing microvesicles, microparticles and large vesicles ranging from ∼100 nm to 1 μm in diameter [14].”

    From Ferroptosis-dependent extracellular vesicles from macrophage contribute to asbestos-induced mesothelial carcinogenesis through loading ferritin (2021) · cites this paper as [14]

    The Nomenclature section describes ectosomes (microparticles/microvesicles) as plasma membrane-derived, supporting the claimed origin. It does not establish that all large EVs form by direct outward budding or have a diameter of approximately 100 nm to 1 μm; instead, it gives >200 nm as an example operational threshold for medium/large EVs and cautions against assuming a unique biogenesis from subtype names. Page numbers are unavailable in our copy. (LLM, conf=0.86)

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  • Vesicle-cell fusion and receptor-mediated endocytosis are associated with cellular response, and macropinocytosis and phagocytosis are for clearance of EVs.

    “Reportedly, vesicle-cell fusion and receptor-mediated endocytosis are associated with cellular response and the other two pathways are for the clearance of EVs [14].”

    From Ferroptosis-dependent extracellular vesicles from macrophage contribute to asbestos-induced mesothelial carcinogenesis through loading ferritin (2021) · cites this paper as [14]

    The EV characterization section (page not provided) says membrane fusion can enable a luminal EV component to function in a recipient cell. It does not establish that receptor-mediated endocytosis is associated with cellular response or that macropinocytosis and phagocytosis serve EV clearance; the Functional studies section instead cautions that EV uptake can be difficult to establish. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

  • The particle-to-protein ratio has been proposed as an indicator for estimating the purity of EV preparations, although its applicability requires careful evaluation since expected ratios can vary depending on factors such as EV origin and isolation method.

    “The particle-to-protein ratio has been proposed as an indicator for estimating the purity of EV preparations [60], although its applicability requires careful evaluation [49,50], since expected ratios can vary depending on multiple factors, such as EV origin and isolation method.”

    From Optimized Wound Healing Assay to Study Extracellular Vesicle-Driven Glioblastoma Cell Migration (2026) · cites this paper as [49]

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Research works printed but not linked: 2

  1. 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.
  2. [8]Reid Y, Storts D, Riss T, 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

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Théry, C., Witwer, K. W., Aikawa, E., Alcaraz, M. J., Anderson, J. D., Andriantsitohaina, R., Antoniou, A., Arab, T., Archer, F., Atkin‐Smith, G. K., Ayre, D. C., Bach, J., Bachurski, D., Baharvand, H., Balaj, L., Baldacchino, S., Bauer, N. N., Baxter, A. A., Bebawy, M., Beckham, C., Bedina Zavec, A., Benmoussa, A., Berardi, A. C., Bergese, P., Bielska, E., Blenkiron, C., Bobis‐Wozowicz, S., Boilard, E., Boireau, W., Bongiovanni, A., Borràs, F. E., Bosch, S., Boulanger, C. M., Breakefield, X., Breglio, A. M., Brennan, M. Á., Brigstock, D. R., Brisson, A., Broekman, M. L., Bromberg, J. F., Bryl‐Górecka, P., Buch, S., Buck, A. H., Burger, D., Busatto, S., Buschmann, D., Bussolati, B., Buzás, E. I., Byrd, J. B., Camussi, G., Carter, D. R., Caruso, S., Chamley, L. W., Chang, Y., Chen, C., Chen, S., Cheng, L., Chin, A. R., Clayton, A., Clerici, S. P., Cocks, A., Cocucci, E., Coffey, R. J., Cordeiro‐da‐Silva, A., Couch, Y., Coumans, F. A., Coyle, B., Crescitelli, R., Criado, M. F., D'Souza‐Schorey, C., Das, S., Datta Chaudhuri, A., de Candia, P., De Santana, E. F., De Wever, O., del Portillo, H. A., Demaret, T., Deville, S., Devitt, A., Dhondt, B., Di Vizio, D., Dieterich, L. C., Dolo, V., Dominguez Rubio, A. P., Dominici, M., Dourado, M. R., Driedonks, T. A., Duarte, F. V., Duncan, H. M., Eichenberger, R. M., Ekström, K., EL Andaloussi, S., Elie‐Caille, C., Erdbrügger, U., Falcón‐Pérez, J. M., Fatima, F., Fish, J. E., Flores‐Bellver, M., Försönits, A., Frelet‐Barrand, A., Fricke, F., Fuhrmann, G., Gabrielsson, S., Gámez‐Valero, A., Gardiner, C., Gärtner, K., Gaudin, R., Gho, Y. S., Giebel, B., Gilbert, C., Gimona, M., Giusti, I., Goberdhan, D. C., Görgens, A., Gorski, S. M., Greening, D. W., Gross, J. C., Gualerzi, A., Gupta, G. N., Gustafson, D., Handberg, A., Haraszti, R. A., Harrison, P., Hegyesi, H., Hendrix, A., Hill, A. F., Hochberg, F. H., Hoffmann, K. F., Holder, B., Holthofer, H., Hosseinkhani, B., Hu, G., Huang, Y., Huber, V., Hunt, S., Ibrahim, A. G., Ikezu, T., Inal, J. M., Isin, M., Ivanova, A., Jackson, H. K., Jacobsen, S., Jay, S. M., Jayachandran, M., Jenster, G., Jiang, L., Johnson, S. M., Jones, J. C., Jong, A., Jovanovic‐Talisman, T., Jung, S., Kalluri, R., Kano, S., Kaur, S., Kawamura, Y., Keller, E. T., Khamari, D., Khomyakova, E., Khvorova, A., Kierulf, P., Kim, K. P., Kislinger, T., Klingeborn, M., Klinke, D. J., Kornek, M., Kosanović, M. M., Kovács, Á. F., Krämer‐Albers, E., Krasemann, S., Krause, M., Kurochkin, I. V., Kusuma, G. D., Kuypers, S., Laitinen, S., Langevin, S. M., Languino, L. R., Lannigan, J., Lässer, C., Laurent, L. C., Lavieu, G., Lázaro‐Ibáñez, E., Le Lay, S., Lee, M., Lee, Y. X. F., Lemos, D. S., Lenassi, M., Leszczynska, A., Li, I. T., Liao, K., Libregts, S. F., Ligeti, E., Lim, R., Lim, S. K., Linē, A., Linnemannstöns, K., Llorente, A., Lombard, C. A., Lorenowicz, M. J., Lörincz, Á. M., Lötvall, J., Lovett, J., Lowry, M. C., Loyer, X., Lu, Q., Lukomska, B., Lunavat, T. R., Maas, S. L., Malhi, H., Marcilla, A., Mariani, J., Mariscal, J., Martens‐Uzunova, E. S., Martin‐Jaular, L., Martinez, M. C., Martins, V. R., Mathieu, M., Mathivanan, S., Maugeri, M., McGinnis, L. K., McVey, M. J., Meckes, D. G., Meehan, K. L., Mertens, I., Minciacchi, V. R., Möller, A., Møller Jørgensen, M., Morales‐Kastresana, A., Morhayim, J., Mullier, F., Muraca, M., Musante, L., Mussack, V., Muth, D. C., Myburgh, K. H., Najrana, T., Nawaz, M., Nazarenko, I., Nejsum, P., Neri, C., Neri, T., Nieuwland, R., Nimrichter, L., Nolan, J. P., Nolte‐'t Hoen, E. N., Noren Hooten, N., O'Driscoll, L., O'Grady, T., O'Loghlen, A., Ochiya, T., Olivier, M., Ortiz, A., Ortiz, L. A., Osteikoetxea, X., Østergaard, O., Ostrowski, M., Park, J., Pegtel, D. M., Peinado, H., Perut, F., Pfaffl, M. W., Phinney, D. G., Pieters, B. C., Pink, R. C., Pisetsky, D. S., Pogge von Strandmann, E., Polakovicova, I., Poon, I. K., Powell, B. H., Prada, I., Pulliam, L., Quesenberry, P., Radeghieri, A., Raffai, R. L., Raimondo, S., Rak, J., Ramirez, M. I., Raposo, G., Rayyan, M. S., Regev‐Rudzki, N., Ricklefs, F. L., Robbins, P. D., Roberts, D. D., Rodrigues, S. C., Rohde, E., Rome, S., Rouschop, K. M., Rughetti, A., Russell, A. E., Saá, P., Sahoo, S., Salas‐Huenuleo, E., Sánchez, C., Saugstad, J. A., Saul, M. J., Schiffelers, R. M., Schneider, R., Schøyen, T. H., Scott, A., Shahaj, E., Sharma, S., Shatnyeva, O., Shekari, F., Shelke, G. V., Shetty, A. K., Shiba, K., Siljander, P. R., Silva, A. M., Skowronek, A., Snyder, O. L., Soares, R. P., Sódar, B. W., Soekmadji, C., Sotillo, J., Stahl, P. D., Stoorvogel, W., Stott, S. L., Strasser, E. F., Swift, S., Tahara, H., Tewari, M., Timms, K., Tiwari, S., Tixeira, R., Tkach, M., Toh, W. S., Tomasini, R., Torrecilhas, A. C., Tosar, J. P., Toxavidis, V., Urbanelli, L., Vader, P., van Balkom, B. W., van der Grein, S. G., Van Deun, J., van Herwijnen, M. J., Van Keuren‐Jensen, K., van Niel, G., van Royen, M. E., van Wijnen, A. J., Vasconcelos, M. H., Vechetti, I. J., Veit, T. D., Vella, L. J., Velot, É., Verweij, F. J., Vestad, B., Viñas, J. L., Visnovitz, T., Vukman, K. V., Wahlgren, J., Watson, D. C., Wauben, M. H., Weaver, A., Webber, J. P., Weber, V., Wehman, A. M., Weiss, D. J., Welsh, J. A., Wendt, S., Wheelock, A. M., Wiener, Z., Witte, L., Wolfram, J., Xagorari, A., Xander, P., Xu, J., Yan, X., Yáñez‐Mó, M., Yin, H., Yuana, Y., Zappulli, V., Zarubova, J., Žėkas, V., Zhang, J., Zhao, Z., Zheng, L., Zheutlin, A. R., Zickler, A. M., Zimmermann, P., Zivkovic, A. M., Zocco, D., & Zuba‐Surma, E. K.
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  • University of Macau (MO)
  • Eindhoven University of Technology (NL)
  • Institute of Physiology CAS Department of Biomaterials and Tissue Engineering BIOCEV Vestec Czech Republic
  • Vilnius University (LT)
  • Guangzhou Medical University School of Pharmaceutical Sciences &amp; the Fifth Affiliated Hospital Key Laboratory of Molecular Target &amp; Clinical Pharmacology Guangzhou China
  • Nanfang Hospital (CN)
  • Exosomics Siena SpA Siena Italy
Corresponding author
  • Théry, Clotilde
  • Witwer, Kenneth W
ORCID
Venue
Journal of Extracellular Vesicles
Publisher
Wiley
Published
2018-11-23
Volume
7
Issue
1
Pages
1535750-1535750
ISSN
2001-3078 (ISSN-L)
DOI
10.1080/20013078.2018.1535750
PMC
PMC6322352
OpenAlex
W2900756811
Cited by
11,099
References
323
Citations by year
2026: 1165 · 2025: 1224 · 2024: 1684 · 2023: 1854 · 2022: 1817 · 2021: 1653 · 2020: 1186 · 2019: 486 · 2018: 7 · 2017: 2 · 2016: 1 · 2013: 4 · 2012: 1
FWCI
296.85
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Extracellular Vesicles (publishedVersion, other-oa)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
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  • GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (submittedVersion, cc-by)
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  • La Trobe University
Funders
  • Agence Nationale de la Recherche (ANR‐11‐LABX‐0043, ANR‐10‐IDEX‐0001‐02 PSL, ANR-11-LABX-0043, ANR-10-IDEX-0001-02 PSL)
  • National Institute on Aging (AG057430)
  • National Institute on Drug Abuse (DA040385, DA047807)
  • Institut National Du Cancer (INCA‐11548)
  • Fondation ARC pour la Recherche sur le Cancer (PGA1 RF20180206962, PJA 20171206453)
  • Sidaction (17‐1‐AAE‐1138, 17-1-AAE-1138)
  • National Institute of Mental Health (MH118164)
  • INSERM, Institut Curie, Ministry of Education (NA)
  • INCa (INCA-11548)
  • Fondation ARC (PGA1 RF20180206962, PJA 20171206453)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Caveolin-1 and cellular processes
Keywords
extracellular vesicles, exosomes, microvesicles, microparticles, ectosome, oncosomes, apoptotic bodies, vesicle biogenesis, vesicle release, vesicle characterization, reporting checklist

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