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1. Dietary-Derived Exosome-like Nanoparticles as Bacterial Modulators: Beyond MicroRNAs.

Author

Manzaneque-López MC, Sánchez-López CM, Pérez-Bermúdez P, Soler C, and Marcilla A

Subjects
Animals, Bacteria metabolism, Vitamins metabolism, Lipids, MicroRNAs metabolism, Exosomes, Nanoparticles
Abstract

There is increasing evidence that food is an important factor that influences the composition of the gut microbiota. Usually, all the attention has been focused on nutrients such as lipids, proteins, vitamins, or polyphenols. However, a pivotal role in these processes has been linked to dietary-derived exosome-like nanoparticles (DELNs). While food macro- and micronutrient composition are largely well established, there is considerable interest in these DELNs and their cargoes. In this sense, traditionally, all the attention was focused on the proteins or miRNAs contained in these vesicles. However, it has been shown that DELNs would also carry other bioactive molecules with a key role in regulating biochemical pathways and/or interactions with the host's gut microbiome affecting intracellular communication. Due to the scarce literature, it is necessary to compile the current knowledge about the antimicrobial capacity of DELNs and its possible molecular mechanisms that will serve as a starting point. For this reason, in this review, we highlight the impact of DENLs on different bacteria species modulating the host gut microbiota or antibacterial properties. It could be concluded that DELNs, isolated from both plant and animal foods, exert gut microbiota modulation. However, the presence of miRNA in the vesicle cargoes is not the only one responsible for this effect. Lipids present in the DELNs membrane or small molecules packed in may also be responsible for apoptosis signaling, inhibition, or growth promoters.

Published
2023
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2. Extracellular vesicles from Trypanosoma cruzi -dendritic cell interaction show modulatory properties and confer resistance to lethal infection as a cell-free based therapy strategy.

Author

Gutierrez BC, Ancarola ME, Volpato-Rossi I, Marcilla A, Ramirez MI, Rosenzvit MC, Cucher M, and Poncini CV

Subjects
Animals, Cell Communication, Trypanosoma cruzi, Extracellular Vesicles, Chagas Disease therapy, Exosomes
Abstract

Extracellular vesicles (EVs) include a heterogeneous group of particles. Microvesicles, apoptotic bodies and exosomes are the most characterized vesicles. They can be distinguished by their size, morphology, origin and molecular composition. To date, increasing studies demonstrate that EVs mediate intercellular communication. EVs reach considerable interest in the scientific community due to their role in diverse processes including antigen-presentation, stimulation of anti-tumoral immune responses, tolerogenic or inflammatory effects. In pathogens, EV shedding is well described in fungi, bacteria, protozoan and helminths parasites. For Trypanosoma cruzi EV liberation and protein composition was previously described. Dendritic cells (DCs), among other cells, are key players promoting the immune response against pathogens and also maintaining self-tolerance. In previous reports we have demonstrate that T. cruzi downregulates DCs immunogenicity in vitro and in vivo . Here we analyze EVs from the in vitro interaction between blood circulating trypomastigotes (Tp) and bone-marrow-derived DCs. We found that Tp incremented the number and the size of EVs in cultures with DCs. EVs displayed some exosome markers and intracellular RNA. Protein analysis demonstrated that the parasite changes the DC protein-EV profile. We observed that EVs from the interaction of Tp-DCs were easily captured by unstimulated-DCs in comparison with EVs from DCs cultured without the parasite, and also modified the activation status of LPS-stimulated DCs. Noteworthy, we found protection in animals treated with EVs-DCs+Tp and challenged with T. cruzi lethal infection. Our goal is to go deep into the molecular characterization of EVs from the DCs-Tp interaction, in order to identify mediators for therapeutic purposes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gutierrez, Ancarola, Volpato-Rossi, Marcilla, Ramirez, Rosenzvit, Cucher and Poncini.)

Published
2022
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3. Exosome levels in human body fluids: A tumor marker by themselves?

Author

Cappello F, Logozzi M, Campanella C, Bavisotto CC, Marcilla A, Properzi F, and Fais S

Subjects
Humans, Neoplasm Recurrence, Local, Neoplasms metabolism, Neoplasms pathology, Biomarkers, Tumor metabolism, Body Fluids metabolism, Exosomes
Abstract

Despite considerable research efforts, the finding of reliable tumor biomarkers remains challenging and unresolved. In recent years a novel diagnostic biomedical tool with high potential has been identified in extracellular nanovesicles or exosomes. They are released by the majority of the cells and contain detailed molecular information on the cell of origin including tumor hallmarks. Exosomes can be isolated from easy accessible body fluids, and most importantly, they can provide several biomarkers, with different levels of specificity. Recent clinical evidence shows that the levels of exosomes released into body fluids may themselves represent a predictive/diagnostic of tumors, discriminating cancer patients from healthy subjects. The aim of this review is to highlight these latest challenging findings to provide novel and groundbreaking ideas for successful tumor early diagnosis and follow-up., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Published
2017
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4. Subcutaneous injection of exosomes reduces symptom severity and mortality induced by Echinostoma caproni infection in BALB/c mice.

Author

Trelis M, Galiano A, Bolado A, Toledo R, Marcilla A, and Bernal D

Subjects
Animals, Antibodies, Helminth biosynthesis, Antigens, Helminth immunology, Disease Models, Animal, Echinostoma immunology, Echinostomiasis mortality, Echinostomiasis prevention & control, Exosomes immunology, Female, Host-Parasite Interactions, Immunoglobulin A immunology, Immunoglobulin G biosynthesis, Immunoglobulin G blood, Immunoglobulin M biosynthesis, Immunomodulation, Injections, Subcutaneous, Interferon-gamma metabolism, Interleukin-10 metabolism, Interleukin-4 metabolism, Intestinal Diseases, Parasitic mortality, Intestinal Diseases, Parasitic prevention & control, Mice, Mice, Inbred BALB C, Random Allocation, Spleen immunology, Transforming Growth Factor beta metabolism, Echinostoma pathogenicity, Echinostomiasis immunology, Exosomes physiology, Intestinal Diseases, Parasitic immunology
Abstract

Recent studies have shown the importance of exosomes in the host-parasite relationship. These vesicles are an important part of the excretory/secretory pathway for proteins with the potential to alter immune responses. Therefore, in the present study, we examined the immunomodulatory role of exosomes in BALB/c mice using Echinostoma caproni as an experimental model of intestinal helminth infection. For this purpose, BALB/c mice were injected twice s.c. with purified exosomes of E. caproni, followed by experimental infection. We report a delay in the development of the parasite in mice immunised with exosomes, a concomitant reduced symptom severity and increased survival upon infection. Immunisations with exosomes evoked systemic antibody responses with high levels of IgM and IgG. IgG1, IgG2b and IgG3 are the subtypes responsible for the IgG increase. These antibodies showed specific recognition of exosomal proteins, indicating that these vesicles carry specific antigens that are involved in the humoral response. The administration of exosomes induced an increase of IFN-γ, IL-4 and TGF-β levels in the spleen of mice prior to infection. The subsequent infection with E. caproni resulted in a further increase of IL-4 and TGF-β, together with an abrupt overproduction of IL-10, suggesting the development of a Th2/Treg immune response. Our results show that the administration of exosomes primes the immune response in the host, which in turn can contribute to tolerance of the invader, reducing the severity of clinical signs in E. caproni infection., (Copyright © 2016 Australian Society for Parasitology. Published by Elsevier Ltd. All rights reserved.)

Published
2016
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5. EVpedia: a community web portal for extracellular vesicles research.

Author

Kim DK, Lee J, Kim SR, Choi DS, Yoon YJ, Kim JH, Go G, Nhung D, Hong K, Jang SC, Kim SH, Park KS, Kim OY, Park HT, Seo JH, Aikawa E, Baj-Krzyworzeka M, van Balkom BW, Belting M, Blanc L, Bond V, Bongiovanni A, Borràs FE, Buée L, Buzás EI, Cheng L, Clayton A, Cocucci E, Dela Cruz CS, Desiderio DM, Di Vizio D, Ekström K, Falcon-Perez JM, Gardiner C, Giebel B, Greening DW, Gross JC, Gupta D, Hendrix A, Hill AF, Hill MM, Nolte-'t Hoen E, Hwang DW, Inal J, Jagannadham MV, Jayachandran M, Jee YK, Jørgensen M, Kim KP, Kim YK, Kislinger T, Lässer C, Lee DS, Lee H, van Leeuwen J, Lener T, Liu ML, Lötvall J, Marcilla A, Mathivanan S, Möller A, Morhayim J, Mullier F, Nazarenko I, Nieuwland R, Nunes DN, Pang K, Park J, Patel T, Pocsfalvi G, Del Portillo H, Putz U, Ramirez MI, Rodrigues ML, Roh TY, Royo F, Sahoo S, Schiffelers R, Sharma S, Siljander P, Simpson RJ, Soekmadji C, Stahl P, Stensballe A, Stępień E, Tahara H, Trummer A, Valadi H, Vella LJ, Wai SN, Witwer K, Yáñez-Mó M, Youn H, Zeidler R, and Gho YS

Subjects
Biomedical Research, Humans, User-Computer Interface, Computational Biology, Database Management Systems, Databases, Factual, Exosomes metabolism, Extracellular Space metabolism, Software
Abstract

Motivation: Extracellular vesicles (EVs) are spherical bilayered proteolipids, harboring various bioactive molecules. Due to the complexity of the vesicular nomenclatures and components, online searches for EV-related publications and vesicular components are currently challenging., Results: We present an improved version of EVpedia, a public database for EVs research. This community web portal contains a database of publications and vesicular components, identification of orthologous vesicular components, bioinformatic tools and a personalized function. EVpedia includes 6879 publications, 172 080 vesicular components from 263 high-throughput datasets, and has been accessed more than 65 000 times from more than 750 cities. In addition, about 350 members from 73 international research groups have participated in developing EVpedia. This free web-based database might serve as a useful resource to stimulate the emerging field of EV research., Availability and Implementation: The web site was implemented in PHP, Java, MySQL and Apache, and is freely available at http://evpedia.info., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Published
2015
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6. Surface analysis of Dicrocoelium dendriticum. The molecular characterization of exosomes reveals the presence of miRNAs.

Author

Bernal D, Trelis M, Montaner S, Cantalapiedra F, Galiano A, Hackenberg M, and Marcilla A

Subjects
Animals, Databases, Protein, Dicrocoelium genetics, Exosomes genetics, Helminth Proteins genetics, MicroRNAs genetics, Proteomics methods, RNA, Helminth genetics, Dicrocoelium metabolism, Exosomes metabolism, Helminth Proteins metabolism, MicroRNAs metabolism, RNA, Helminth metabolism
Abstract

With the aim of characterizing the molecules involved in the interaction of Dicrocoelium dendriticum adults and the host, we have performed proteomic analyses of the external surface of the parasite using the currently available datasets including the transcriptome of the related species Echinostoma caproni. We have identified 182 parasite proteins on the outermost surface of D. dendriticum. The presence of exosome-like vesicles in the ESP of D. dendriticum and their components has also been characterized. Using proteomic approaches, we have characterized 84 proteins in these vesicles. Interestingly, we have detected miRNA in D. dendriticum exosomes, thus representing the first report of miRNA in helminth exosomes., Biological Significance: In order to identify potential targets for intervention against parasitic helminths, we have analyzed the surface of the parasitic helminth Dicrocoelium dendriticum. Along with the proteomic analyses of the outermost layer of the parasite, our work describes the molecular characterization of the exosomes of D. dendriticum. Our proteomic data confirm the improvement of protein identification from "non-model organisms" like helminths, when using different search engines against a combination of available databases. In addition, this work represents the first report of miRNAs in parasitic helminth exosomes. These vesicles can pack specific proteins and RNAs providing stability and resistance to RNAse digestion in body fluids, and provide a way to regulate host-parasite interplay. The present data should provide a solid foundation for the development of novel methods to control this non-model organism and related parasites. This article is part of a Special Issue entitled: Proteomics of non-model organisms., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Published
2014
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7. Vesiclepedia: a compendium for extracellular vesicles with continuous community annotation.

Author

Kalra H, Simpson RJ, Ji H, Aikawa E, Altevogt P, Askenase P, Bond VC, Borràs FE, Breakefield X, Budnik V, Buzas E, Camussi G, Clayton A, Cocucci E, Falcon-Perez JM, Gabrielsson S, Gho YS, Gupta D, Harsha HC, Hendrix A, Hill AF, Inal JM, Jenster G, Krämer-Albers EM, Lim SK, Llorente A, Lötvall J, Marcilla A, Mincheva-Nilsson L, Nazarenko I, Nieuwland R, Nolte-'t Hoen EN, Pandey A, Patel T, Piper MG, Pluchino S, Prasad TS, Rajendran L, Raposo G, Record M, Reid GE, Sánchez-Madrid F, Schiffelers RM, Siljander P, Stensballe A, Stoorvogel W, Taylor D, Thery C, Valadi H, van Balkom BW, Vázquez J, Vidal M, Wauben MH, Yáñez-Mó M, Zoeller M, and Mathivanan S

Subjects
Apoptosis, Databases as Topic, Exosomes metabolism, Extracellular Space metabolism, Research
Abstract

Extracellular vesicles (EVs) are membraneous vesicles released by a variety of cells into their microenvironment. Recent studies have elucidated the role of EVs in intercellular communication, pathogenesis, drug, vaccine and gene-vector delivery, and as possible reservoirs of biomarkers. These findings have generated immense interest, along with an exponential increase in molecular data pertaining to EVs. Here, we describe Vesiclepedia, a manually curated compendium of molecular data (lipid, RNA, and protein) identified in different classes of EVs from more than 300 independent studies published over the past several years. Even though databases are indispensable resources for the scientific community, recent studies have shown that more than 50% of the databases are not regularly updated. In addition, more than 20% of the database links are inactive. To prevent such database and link decay, we have initiated a continuous community annotation project with the active involvement of EV researchers. The EV research community can set a gold standard in data sharing with Vesiclepedia, which could evolve as a primary resource for the field., Competing Interests: The authors have declared that no competing interests exist.

Published
2012
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8. Extracellular vesicles from parasitic helminths contain specific excretory/secretory proteins and are internalized in intestinal host cells.

Author

Marcilla A, Trelis M, Cortés A, Sotillo J, Cantalapiedra F, Minguez MT, Valero ML, Sánchez del Pino MM, Muñoz-Antoli C, Toledo R, and Bernal D

Subjects
Animals, Cell Line, Tumor, Echinostoma ultrastructure, Echinostomiasis metabolism, Echinostomiasis parasitology, Fasciola hepatica ultrastructure, Fascioliasis metabolism, Fascioliasis parasitology, Humans, Intestinal Mucosa cytology, Intestinal Mucosa metabolism, Rats, Echinostoma physiology, Exosomes metabolism, Fasciola hepatica physiology, Helminth Proteins metabolism, Host-Parasite Interactions, Intestinal Mucosa parasitology
Abstract

The study of host-parasite interactions has increased considerably in the last decades, with many studies focusing on the identification of parasite molecules (i.e. surface or excretory/secretory proteins (ESP)) as potential targets for new specific treatments and/or diagnostic tools. In parallel, in the last few years there have been significant advances in the field of extracellular vesicles research. Among these vesicles, exosomes of endocytic origin, with a characteristic size ranging from 30-100 nm, carry several atypical secreted proteins in different organisms, including parasitic protozoa. Here, we present experimental evidence for the existence of exosome-like vesicles in parasitic helminths, specifically the trematodes Echinostoma caproni and Fasciola hepatica. These microvesicles are actively released by the parasites and are taken up by host cells. Trematode extracellular vesicles contain most of the proteins previously identified as components of ESP, as confirmed by proteomic, immunogold labeling and electron microscopy studies. In addition to parasitic proteins, we also identify host proteins in these structures. The existence of extracellular vesicles explains the secretion of atypical proteins in trematodes, and the demonstration of their uptake by host cells suggests an important role for these structures in host-parasite communication, as described for other infectious agents.

Published
2012
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10. The Potential Roles of Extracellular Vesicles as Biomarkers for Parkinson's Disease: A Systematic Review.

Author

Valencia, Jessica, Ferreira, Marta, Merino-Torres, J. Francisco, Marcilla, Antonio, and Soriano, Jose M.

Subjects
PARKINSON'S disease, EXTRACELLULAR vesicles, DOPAMINERGIC neurons, SUBSTANTIA nigra, BIOMARKERS, ALPHA-synuclein
Abstract

Parkinson's disease (PD) is a slowly progressive neurodegenerative disorder, characterized by the misfolding and aggregation of α-synuclein (α-syn) into Lewy bodies and the degeneration of dopaminergic neurons in the substantia nigra pars compacta. The urge for an early diagnosis biomarker comes from the fact that clinical manifestations of PD are estimated to appear once the substantia nigra has deteriorated and there has been a reduction of the dopamine levels from the striatum. Nowadays, extracellular vesicles (EVs) play an important role in the pathogenesis of neuro-degenerative diseases as PD. A systematic review dated August 2022 was carried out with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses with the aim to analyze the potential role of EVs as biomarkers for PD. From a total of 610 articles retrieved, 29 were eligible. This review discusses the role of EVs biochemistry and their cargo proteins, such as α-syn and DJ-1 among others, detected by a proteomic analysis as well as miRNAs and lncRNAs, as potential biomarkers that can be used to create standardized protocols for early PD diagnosis as well as to evaluate disease severity and progression. [ABSTRACT FROM AUTHOR]

Published
2022
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11. Molecular Profile Study of Extracellular Vesicles for the Identification of Useful Small "Hit" in Cancer Diagnosis.

Author

Alberti, Giusi, Sánchez-López, Christian M., Andres, Alexia, Santonocito, Radha, Campanella, Claudia, Cappello, Francesco, and Marcilla, Antonio

Subjects
EXTRACELLULAR vesicles, CANCER diagnosis, TUMOR markers, CANCER invasiveness, METASTASIS, EXOSOMES, CIRCULATING tumor DNA
Abstract

Tumor-secreted extracellular vesicles (EVs) are the main mediators of cell-cell communication, permitting cells to exchange proteins, lipids, and metabolites in varying physiological and pathological conditions. They contain signature tumor-derived molecules that reflect the intracellular status of their cell of origin. Recent studies have shown that tumor cell-derived EVs can aid in cancer metastasis through the modulation of the tumor microenvironment, suppression of the immune system, pre-metastatic niche formation, and subsequent metastasis. EVs can easily be isolated from a variety of biological fluids, and their content makes them useful biomarkers for the diagnosis, prognosis, monitorization of cancer progression, and response to treatment. This review aims to explore the biomarkers of cancer cell-derived EVs obtained from liquid biopsies, in order to understand cancer progression and metastatic evolution for early diagnosis and precision therapy. [ABSTRACT FROM AUTHOR]

Published
2021
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12. 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

Author

Théry, Clotilde, Witwer, Kenneth W, Aikawa, Elena, Alcaraz, Maria Jose, Anderson, Johnathon D, Andriantsitohaina, Ramaroson, Antoniou, Anna, Arab, Tanina, Archer, Fabienne, Atkin-Smith, Georgia K, Ayre, D Craig, Bach, Jean-Marie, Bachurski, Daniel, Baharvand, Hossein, Balaj, Leonora, Baldacchino, Shawn, Bauer, Natalie N, Baxter, Amy A, Bebawy, Mary, Beckham, Carla, Bedina Zavec, Apolonija, Benmoussa, Abderrahim, Berardi, Anna C, Bergese, Paolo, Bielska, Ewa, Blenkiron, Cherie, Bobis-Wozowicz, Sylwia, Boilard, Eric, Boireau, Wilfrid, Bongiovanni, Antonella, Borràs, Francesc E, Bosch, Steffi, Boulanger, Chantal M, Breakefield, Xandra, Breglio, Andrew M, Brennan, Meadhbh Á, Brigstock, David R, Brisson, Alain, Broekman, Marike Ld, Bromberg, Jacqueline F, Bryl-Górecka, Paulina, Buch, Shilpa, Buck, Amy H, Burger, Dylan, Busatto, Sara, Buschmann, Dominik, Bussolati, Benedetta, Buzás, Edit I, Byrd, James Bryan, Camussi, Giovanni, Carter, David Rf, Caruso, Sarah, Chamley, Lawrence W, Chang, Yu-Ting, Chen, Chihchen, Chen, Shuai, Cheng, Lesley, Chin, Andrew R, Clayton, Aled, Clerici, Stefano P, Cocks, Alex, Cocucci, Emanuele, Coffey, Robert J, Cordeiro-da-Silva, Anabela, Couch, Yvonne, Coumans, Frank Aw, Coyle, Beth, Crescitelli, Rossella, Criado, Miria Ferreira, D'Souza-Schorey, Crislyn, Das, Saumya, Datta Chaudhuri, Amrita, de Candia, Paola, De Santana, Eliezer F, De Wever, Olivier, Del Portillo, Hernando A, Demaret, Tanguy, Deville, Sarah, Devitt, Andrew, Dhondt, Bert, Di Vizio, Dolores, Dieterich, Lothar C, Dolo, Vincenza, Dominguez Rubio, Ana Paula, Dominici, Massimo, Dourado, Mauricio R, Driedonks, Tom Ap, Duarte, Filipe V, Duncan, Heather M, Eichenberger, Ramon M, Ekström, Karin, El Andaloussi, Samir, Elie-Caille, Celine, Erdbrügger, Uta, Falcón-Pérez, Juan M, Fatima, Farah, Fish, Jason E, Flores-Bellver, Miguel, Försönits, András, Frelet-Barrand, Annie, Fricke, Fabia, Fuhrmann, Gregor, Gabrielsson, Susanne, Gámez-Valero, Ana, Gardiner, Chris, Gärtner, Kathrin, Gaudin, Raphael, Gho, Yong Song, Giebel, Bernd, Gilbert, Caroline, Gimona, Mario, Giusti, Ilaria, Goberdhan, Deborah Ci, Görgens, André, Gorski, Sharon M, Greening, David W, Gross, Julia Christina, Gualerzi, Alice, Gupta, Gopal N, Gustafson, Dakota, Handberg, Aase, Haraszti, Reka A, Harrison, Paul, Hegyesi, Hargita, Hendrix, An, Hill, Andrew F, Hochberg, Fred H, Hoffmann, Karl F, Holder, Beth, Holthofer, Harry, Hosseinkhani, Baharak, Hu, Guoku, Huang, Yiyao, Huber, Veronica, Hunt, Stuart, Ibrahim, Ahmed Gamal-Eldin, Ikezu, Tsuneya, Inal, Jameel M, Isin, Mustafa, Ivanova, Alena, Jackson, Hannah K, Jacobsen, Soren, Jay, Steven M, Jayachandran, Muthuvel, Jenster, Guido, Jiang, Lanzhou, Johnson, Suzanne M, Jones, Jennifer C, Jong, Ambrose, Jovanovic-Talisman, Tijana, Jung, Stephanie, Kalluri, Raghu, Kano, Shin-Ichi, Kaur, Sukhbir, Kawamura, Yumi, Keller, Evan T, Khamari, Delaram, Khomyakova, Elena, Khvorova, Anastasia, Kierulf, Peter, Kim, Kwang Pyo, Kislinger, Thomas, Klingeborn, Mikael, Klinke, David J, Kornek, Miroslaw, Kosanović, Maja M, Kovács, Árpád Ferenc, Krämer-Albers, Eva-Maria, Krasemann, Susanne, Krause, Mirja, Kurochkin, Igor V, Kusuma, Gina D, Kuypers, Sören, Laitinen, Saara, Langevin, Scott M, Languino, Lucia R, Lannigan, Joanne, Lässer, Cecilia, Laurent, Louise C, Lavieu, Gregory, Lázaro-Ibáñez, Elisa, Le Lay, Soazig, Lee, Myung-Shin, Lee, Yi Xin Fiona, Lemos, Debora S, Lenassi, Metka, Leszczynska, Aleksandra, Li, Isaac Ts, Liao, Ke, Libregts, Sten F, Ligeti, Erzsebet, Lim, Rebecca, Lim, Sai Kiang, Linē, Aija, Linnemannstöns, Karen, Llorente, Alicia, Lombard, Catherine A, Lorenowicz, Magdalena J, Lörincz, Ákos M, Lötvall, Jan, Lovett, Jason, Lowry, Michelle C, Loyer, Xavier, Lu, Quan, Lukomska, Barbara, Lunavat, Taral R, Maas, Sybren Ln, Malhi, Harmeet, Marcilla, Antonio, Mariani, Jacopo, Mariscal, Javier, Martens-Uzunova, Elena S, Martin-Jaular, Lorena, Martinez, M Carmen, Martins, Vilma Regina, Mathieu, Mathilde, Mathivanan, Suresh, Maugeri, Marco, McGinnis, Lynda K, McVey, Mark J, Meckes, David G, Meehan, Katie L, Mertens, Inge, Minciacchi, Valentina R, Möller, Andreas, Møller Jørgensen, Malene, Morales-Kastresana, Aizea, Morhayim, Jess, Mullier, François, Muraca, Maurizio, Musante, Luca, Mussack, Veronika, Muth, Dillon C, Myburgh, Kathryn H, Najrana, Tanbir, Nawaz, Muhammad, Nazarenko, Irina, Nejsum, Peter, Neri, Christian, Neri, Tommaso, Nieuwland, Rienk, Nimrichter, Leonardo, Nolan, John P, Nolte-'t Hoen, Esther NM, Noren Hooten, Nicole, O'Driscoll, Lorraine, O'Grady, Tina, O'Loghlen, Ana, Ochiya, Takahiro, Olivier, Martin, Ortiz, Alberto, Ortiz, Luis A, Osteikoetxea, Xabier, Østergaard, Ole, Ostrowski, Matias, Park, Jaesung, Pegtel, D Michiel, Peinado, Hector, Perut, Francesca, Pfaffl, Michael W, Phinney, Donald G, Pieters, Bartijn Ch, Pink, Ryan C, Pisetsky, David S, Pogge von Strandmann, Elke, Polakovicova, Iva, Poon, Ivan Kh, Powell, Bonita H, Prada, Ilaria, Pulliam, Lynn, Quesenberry, Peter, Radeghieri, Annalisa, Raffai, Robert L, Raimondo, Stefania, Rak, Janusz, Ramirez, Marcel I, Raposo, Graça, Rayyan, Morsi S, Regev-Rudzki, Neta, Ricklefs, Franz L, Robbins, Paul D, Roberts, David D, Rodrigues, Silvia C, Rohde, Eva, Rome, Sophie, Rouschop, Kasper Ma, Rughetti, Aurelia, Russell, Ashley E, Saá, Paula, Sahoo, Susmita, Salas-Huenuleo, Edison, Sánchez, Catherine, Saugstad, Julie A, Saul, Meike J, Schiffelers, Raymond M, Schneider, Raphael, Schøyen, Tine Hiorth, Scott, Aaron, Shahaj, Eriomina, Sharma, Shivani, Shatnyeva, Olga, Shekari, Faezeh, Shelke, Ganesh Vilas, Shetty, Ashok K, Shiba, Kiyotaka, Siljander, Pia R-M, Silva, Andreia M, Skowronek, Agata, Snyder, Orman L, Soares, Rodrigo Pedro, Sódar, Barbara W, Soekmadji, Carolina, Sotillo, Javier, Stahl, Philip D, Stoorvogel, Willem, Stott, Shannon L, Strasser, Erwin F, Swift, Simon, Tahara, Hidetoshi, Tewari, Muneesh, Timms, Kate, Tiwari, Swasti, Tixeira, Rochelle, Tkach, Mercedes, Toh, Wei Seong, Tomasini, Richard, Torrecilhas, Ana Claudia, Tosar, Juan Pablo, Toxavidis, Vasilis, Urbanelli, Lorena, Vader, Pieter, van Balkom, Bas Wm, van der Grein, Susanne G, Van Deun, Jan, van Herwijnen, Martijn Jc, Van Keuren-Jensen, Kendall, van Niel, Guillaume, van Royen, Martin E, van Wijnen, Andre J, Vasconcelos, M Helena, Vechetti, Ivan J, Veit, Tiago D, Vella, Laura J, Velot, Émilie, Verweij, Frederik J, Vestad, Beate, Viñas, Jose L, Visnovitz, Tamás, Vukman, Krisztina V, Wahlgren, Jessica, Watson, Dionysios C, Wauben, Marca Hm, Weaver, Alissa, Webber, Jason P, Weber, Viktoria, Wehman, Ann M, Weiss, Daniel J, Welsh, Joshua A, Wendt, Sebastian, Wheelock, Asa M, Wiener, Zoltán, Witte, Leonie, Wolfram, Joy, Xagorari, Angeliki, Xander, Patricia, Xu, Jing, Yan, Xiaomei, Yáñez-Mó, María, Yin, Hang, Yuana, Yuana, Zappulli, Valentina, Zarubova, Jana, Žėkas, Vytautas, Zhang, Jian-Ye, Zhao, Zezhou, Zheng, Lei, Zheutlin, Alexander R, Zickler, Antje M, Zimmermann, Pascale, Zivkovic, Angela M, Zocco, Davide, Zuba-Surma, Ewa K, dB&C I&I, LS Celbiologie-Algemeen, Celbiologie, Afd Pharmaceutics, Sub General Pharmaceutics, Sub Biomol.Mass Spect. and Proteomics, Afd Pharmacology, Urology, Pathology, Medical Oncology, Immunité et cancer, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Johns Hopkins University School of Medicine [Baltimore], Stress Oxydant et Pathologies Métaboliques (SOPAM), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192 (PRISM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Infections Virales et Pathologie Comparée - UMR 754 (IVPC), Institut National de la Recherche Agronomique (INRA)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Immuno-Endocrinologie Cellulaire et Moléculaire [Nantes] (IECM), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Department for Molecular Biology and Nanobiotechnology, National Institute of chemitry, Slovenia, Biologie, génétique et thérapies ostéoarticulaires et respiratoires (BIOTARGEN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Immuno-Endocrinologie Cellulaire et Moléculaire (IECM), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes, Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie des Adaptations Nutritionnelles (PhAN), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Imagerie Moléculaire et Nanobiotechnologies - Institut Européen de Chimie et Biologie (IECB), Université Sciences et Technologies - Bordeaux 1-Centre National de la Recherche Scientifique (CNRS), Molecular Biotechnology Center, Università degli studi di Torino = University of Turin (UNITO), Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Centre for Sustainable Tropical Fisheries and Aquaculture, James Cook University (JCU), Department of Oncology - Pathology, Cancer Center Karolinska [Karolinska Institutet] (CCK), Karolinska Institutet [Stockholm]-Karolinska Institutet [Stockholm], Departamento de Ciências Biológicas, Universidade do Porto = University of Porto, Laboratory of Experimental Cancer Research, Department of Radiation Oncology and Experimental Cancer Research, Cancer Research Institute Ghent (CRIG), Universiteit Gent = Ghent University [Belgium] (UGENT), Department of Medical and Surgical Sciences for Children and Adults [Modena, Italy] (Laboratory of Cellular Therapy), Università degli Studi di Modena e Reggio Emilia (UNIMORE), Clinical Research Center, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Huddinge, Sweden, Karolinska Institutet [Stockholm]-Karolinska University Hospital [Stockholm], Center for Cooperative Research in Biosciences (CIC bioGUNE), Partner site Munich, German Centre for Infection Research (DZIF), Institute for Transfusion Medicine, University Hospital Essen, Universität Duisburg-Essen [Essen], Mécanismes Adaptatifs et Evolution (MECADEV), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Psychiatry, Institute of Biological, Environmental and Rural Sciences (IBERS), Aberystwyth University, Department of Bacteriology and Immunology [Helsinki], Haartman Institute [Helsinki], Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Rigshospitalet [Copenhagen], Copenhagen University Hospital, Dalhousie University [Halifax], Department of Biology, Molecular Cell Biology, University of Mainz, Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU), Glycobiologie et signalisation cellulaire, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, University of Gothenburg (GU), Universidad de Alicante, École supérieure du professorat et de l'éducation - Académie de Créteil (UPEC ESPE Créteil), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), University of Antwerp (UA), Université Catholique de Louvain = Catholic University of Louvain (UCL), Research Institute, IRCCS Ospedale Pediatrico Bambino Gesù [Roma], Department of Veterinary Disease Biology [Copenhagen], Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), Biologie et Pathologie du Neurone (Brain-C), Adaptation Biologique et Vieillissement = Biological Adaptation and Ageing (B2A), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Mathematics and Statistics, American University, University of Pretoria [South Africa], Ecole des Ingénieurs de la Ville de Paris (EIVP), Universitat Pompeu Fabra [Barcelona] (UPF), Instituto de Investigaciones Biomedicas, Universidad Nacional Autónoma de México (UNAM), Istituto Ortopedico Rizzoli, Department of Molecular Therapeutics, The Scripps Research Institute, Laboratoire d'Informatique de Grenoble (LIG ), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Montreal Children's Hospital, McGill University Health Center [Montreal] (MUHC), Compartimentation et dynamique cellulaires (CDC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Curie [Paris]-Centre National de la Recherche Scientifique (CNRS), National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cardiovascular Research Center, Massachusetts General Hospital [Boston], University Medical Center [Utrecht], University of Toronto, Fiocruz Minas - René Rachou Research Center / Instituto René Rachou [Belo Horizonte, Brésil], Fundação Oswaldo Cruz (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Federal University of Sao Paulo (Unifesp), Functional Genomics / Genómica Funcional [Montevideo], Institut Pasteur de Montevideo, Dipartimento di Medicina Sperimentale e Scienze Biochimiche, Università degli Studi di Perugia (UNIPG), Hospital Santa Cristina Instituto de Investigación Sanitaria Princesa C, Unidad de Investigación, Institut Curie [Paris]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Department of Physiology, University of California [San Francisco] (UCSF), University of California-University of California, University of Vermont [Burlington], Peking University [Beijing], Shandong Agricultural University (SDAU), State Key Laboratory of Quality Research in Chinese Medicine Taipa, Macau SAR, (Institute of Chinese Medical Sciences), Human Genetics, Universität Ulm - Ulm University [Ulm, Allemagne], INSERM, Institut Curie, INCa [INCA-11548], French National Research Agency [ANR-10-IDEX-0001-02 PSL*, ANR-11-LABX-0043], SIDACTION [17-1-AAE-1138], Fondation ARC [PGA1 RF20180206962, PJA 20171206453], NIDA [DA040385, DA047807], Ministry of Education, NIA [AG057430], NIMH [MH118164], Institut National de la Recherche Agronomique (INRA)-École Pratique des Hautes Études (EPHE), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN), Université Sciences et Technologies - Bordeaux 1 (UB)-Centre National de la Recherche Scientifique (CNRS), Universiteit Gent = Ghent University (UGENT), Università degli Studi di Modena e Reggio Emilia = University of Modena and Reggio Emilia (UNIMORE), Universität Duisburg-Essen = University of Duisburg-Essen [Essen], Biotechnology and Biological Sciences Research Council (BBSRC)-Aberystwyth University, University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), Universidad Nacional Autónoma de México = National Autonomous University of Mexico (UNAM), The Scripps Research Institute [La Jolla, San Diego], Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), Università degli Studi di Perugia = University of Perugia (UNIPG), Instituto de Investigacion Sanitaria del Hospital de la Princesa, Hospital Universitario de La Princesa, University of California [San Francisco] (UC San Francisco), University of California (UC)-University of California (UC), ANR-17-CE09-0025,MADNESS,Une approche microfluidique générique pour la qualification des nanoparticules biologiques(2017), Institut National de la Recherche Agronomique (INRA)-École pratique des hautes études (EPHE)-Université Claude Bernard Lyon 1 (UCBL), Biomedical Engineering and Physics, ACS - Atherosclerosis & ischemic syndromes, ACS - Microcirculation, Laboratory Specialized Diagnostics & Research, Radiotherapie, RS: GROW - R2 - Basic and Translational Cancer Biology, Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Université Nice Sophia Antipolis (... - 2019) (UNS), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), Ecole Nationale Vétérinaire de Nantes-Université de Nantes (UN)-Institut National de la Recherche Agronomique (INRA), Università degli studi di Torino (UNITO), Universidade do Porto, University of Helsinki-University of Helsinki-Faculty of Medecine [Helsinki], University of Helsinki-University of Helsinki, Johannes Gutenberg - Universität Mainz (JGU), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Université Pierre et Marie Curie - Paris 6 (UPMC), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Université de Toronto [Canada], Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192 (PRISM), Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Université de Franche-Comté (UFC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Technologie de Belfort-Montbeliard (UTBM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM), Universidade do Porto [Porto], Ghent University [Belgium] (UGENT), FEMTO-ST Institute, Université de Technologie de Belfort-Montbeliard (UTBM)-Université de Franche-Comté (UFC)-CNRS : UMR6174, Mécanismes adaptatifs : des organismes aux communautés (MECADEV), Centre National de la Recherche Scientifique (CNRS)-Muséum national d'Histoire naturelle (MNHN), Johannes Gutenberg - University of Mainz (JGU), Université Catholique de Louvain (UCL), Universitat Pompeu Fabra [Barcelona], Laboratoire d'Informatique de Grenoble (LIG), Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Centre National de la Recherche Scientifique (CNRS)-Institut Curie-Université Pierre et Marie Curie - Paris 6 (UPMC), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Laboratoire Réactions et Génie des Procédés (LRGP), Fiocruz Minas - René Rachou Research Center / Instituto René Rachou, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Functional Genomics Unit, Institut Curie-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), University of Vermont College of Medicine [Burlington, VT, USA], Extracellular Vesicles, Molecular and Integrative Biosciences Research Programme, Thery, 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. -M., 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., Borras, F. E., Bosch, S., Boulanger, C. M., Breakefield, X., Breglio, A. M., Brennan, M. A., Brigstock, D. R., Brisson, A., Broekman, M. L. D., Bromberg, J. F., Bryl-Gorecka, P., Buch, S., Buck, A. H., Burger, D., Busatto, S., Buschmann, D., Bussolati, B., Buzas, E. I., Byrd, J. B., Camussi, G., Carter, D. R. F., Caruso, S., Chamley, L. W., Chang, Y. -T., Chaudhuri, A. D., 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. W., Coyle, B., Crescitelli, R., Criado, M. F., D'Souza-Schorey, C., Das, S., 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. P., Duarte, F. V., Duncan, H. M., Eichenberger, R. M., Ekstrom, K., EL Andaloussi, S., Elie-Caille, C., Erdbrugger, U., Falcon-Perez, J. M., Fatima, F., Fish, J. E., Flores-Bellver, M., Forsonits, A., Frelet-Barrand, A., Fricke, F., Fuhrmann, G., Gabrielsson, S., Gamez-Valero, A., Gardiner, C., Gartner, K., Gaudin, R., Gho, Y. S., Giebel, B., Gilbert, C., Gimona, M., Giusti, I., Goberdhan, D. C. I., Gorgens, 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. -E., 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. -I., 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., Kosanovic, M. M., Kovacs, A. F., Kramer-Albers, E. -M., Krasemann, S., Krause, M., Kurochkin, I. V., Kusuma, G. D., Kuypers, S., Laitinen, S., Langevin, S. M., Languino, L. R., Lannigan, J., Lasser, C., Laurent, L. C., Lavieu, G., Lazaro-Ibanez, E., Le Lay, S., Lee, M. -S., Lee, Y. X. F., Lemos, D. S., Lenassi, M., Leszczynska, A., Li, I. T. S., Liao, K., Libregts, S. F., Ligeti, E., Lim, R., Lim, S. K., Line, A., Linnemannstons, K., Llorente, A., Lombard, C. A., Lorenowicz, M. J., Lorincz, A. M., Lotvall, J., Lovett, J., Lowry, M. C., Loyer, X., Lu, Q., Lukomska, B., Lunavat, T. R., Maas, S. L. N., 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., Moller, A., Moller Jorgensen, 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. M., Noren Hooten, N., O'Driscoll, L., O'Grady, T., O'Loghlen, A., Ochiya, T., Olivier, M., Ortiz, A., Ortiz, L. A., Osteikoetxea, X., Ostegaard, O., Ostrowski, M., Park, J., Pegtel, D. M., Peinado, H., Perut, F., Pfaffl, M. W., Phinney, D. G., Pieters, B. C. H., Pink, R. C., Pisetsky, D. S., Pogge von Strandmann, E., Polakovicova, I., Poon, I. K. H., 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. A., Rughetti, A., Russell, A. E., Saa, P., Sahoo, S., Salas-Huenuleo, E., Sanchez, C., Saugstad, J. A., Saul, M. J., Schiffelers, R. M., Schneider, R., Schoyen, T. H., Scott, A., Shahaj, E., Sharma, S., Shatnyeva, O., Shekari, F., Shelke, G. V., Shetty, A. K., Shiba, K., Siljander, P. R. -M., Silva, A. M., Skowronek, A., Snyder, O. L., Soares, R. P., Sodar, 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. M., van der Grein, S. G., Van Deun, J., van Herwijnen, M. J. C., 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, E., Verweij, F. J., Vestad, B., Vinas, J. L., Visnovitz, T., Vukman, K. V., Wahlgren, J., Watson, D. C., Wauben, M. H. M., 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., Yanez-Mo, M., Yin, H., Yuana, Y., Zappulli, V., Zarubova, J., Zekas, V., Zhang, J. -Y., Zhao, Z., Zheng, L., Zheutlin, A. R., Zickler, A. M., Zimmermann, P., Zivkovic, A. M., Zocco, D., Zuba-Surma, E. K., dB&C I&I, LS Celbiologie-Algemeen, Celbiologie, Afd Pharmaceutics, Sub General Pharmaceutics, Sub Biomol.Mass Spect. and Proteomics, Afd Pharmacology, CCA - Imaging and biomarkers, Amsterdam Neuroscience - Neuroinfection & -inflammation, and Amsterdam Neuroscience - Cellular & Molecular Mechanisms

Subjects
ectosome, ectosomes, exosomes, extracellular vesicles, guidelines, microparticles, microvesicles, minimal information requirements, reproducibility, rigor, standardization, Histology, Cell Biology, [SDV]Life Sciences [q-bio], size-exclusion, Medicine and Health Sciences, CELL-DERIVED MICROPARTICLES, FIELD-FLOW FRACTIONATION, requirements, circulating, ComputingMilieux_MISCELLANEOUS, Manchester Cancer Research Centre, lcsh:Cytology, PROSTATE-CANCER, microparticle, Cell interaction, microvesicle, chromatography, Position Paper, guideline, Life Sciences & Biomedicine, ectosomes, exosomes, extracellular vesicles, guidelines, microparticles, microvesicles, minimal information requirements, reproducibility, rigor, standardization, MEMBRANE-VESICLES, FETAL BOVINE, Ectosomes, Exosomes, Extracellular Vesicles, Guidelines, Microparticles, Microvesicles, Minimal Information Requirements, Reproducibility, Rigor, Standardization, CIRCULATING MICROPARTICLES, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, ddc:570, exosome, SURFACE-PLASMON RESONANCE, ddc:610, lcsh:QH573-671, Biology, Interacció cel·lular, Science & Technology, ResearchInstitutes_Networks_Beacons/mcrc, Cell membranes, HUMAN URINARY EXOSOMES, PREANALYTICAL PARAMETERS, minimal information requirement, SIZE-EXCLUSION CHROMATOGRAPHY, 1182 Biochemistry, cell and molecular biology, extracellular vesicle, Human medicine, Membranes cel·lulars
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.

Published
2018

13. Hsa-miR-30d, secreted by the human endometrium, is taken up by the pre-implantation embryo and might modify its transcriptome.

Author

Vilella, Felipe, Moreno-Moya, Juan M., Balaguer, Nuria, Grasso, Alessia, Herrero, Maria, Martínez, Sebastian, Marcilla, Antonio, and Simo'n, Carlos

Subjects
EMBRYO implantation, ENDOMETRIUM, GENE expression, EXOSOMES, CELL adhesion molecules, MICRORNA
Abstract

During embryo implantation, the blastocyst interacts with and regulates the endometrium, and endometrial fluid secreted by the endometrial epithelium nurtures the embryo. Here, we propose that maternal microRNAs (miRNAs) might act as transcriptomic modifier of the pre-implantation embryo. Microarray profiling revealed that six of 27 specific, maternal miRNAs were differentially expressed in the human endometrial epithelium during the window of implantation - a brief phase of endometrial receptivity to the blastocyst - and were released into the endometrial fluid. Further investigation revealed that hsa-miR-30d, the expression levels of which were most significantly upregulated, was secreted as an exosome-associated molecule. Exosome-associated and free hsa-miR-30d was internalized by mouse embryos via the trophectoderm, resulting in an indirect overexpression of genes encoding for certain molecules involved in the murine embryonic adhesion phenomenon - Itgb3, Itga7 and Cdh5. Indeed, this finding was supported by evidence in vitro: treating murine embryos with miR-30d resulted in a notable increase in embryo adhesion. Our results suggest a model in which maternal endometrial miRNAs act as transcriptomic modifiers of the preimplantation embryo. [ABSTRACT FROM AUTHOR]

Published
2015
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14. Extracellular vesicles in parasitic diseases.

Author

Marcilla, Antonio, Martin‐Jaular, Lorena, Trelis, Maria, de Menezes‐Neto, Armando, Osuna, Antonio, Bernal, Dolores, Fernandez‐Becerra, Carmen, Almeida, Igor C., and del Portillo, Hernando A.

Abstract

Parasitic diseases affect billions of people and are considered a major public health issue. Close to 400 species are estimated to parasitize humans, of which around 90 are responsible for great clinical burden and mortality rates. Unfortunately, they are largely neglected as they are mainly endemic to poor regions. Of relevance to this review, there is accumulating evidence of the release of extracellular vesicles (EVs) in parasitic diseases, acting both in parasite–parasite inter‐communication as well as in parasite–host interactions. EVs participate in the dissemination of the pathogen and play a role in the regulation of the host immune systems. Production of EVs from parasites or parasitized cells has been described for a number of parasitic infections. In this review, we provide the most relevant findings of the involvement of EVs in intercellular communication, modulation of immune responses, involvement in pathology, and their potential as new diagnostic tools and therapeutic agents in some of the major human parasitic pathogens. [ABSTRACT FROM AUTHOR]

Published
2014
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15. First Symposium of "Grupo Español de Investigación en Vesículas Extracelulares (GEIVEX)", Segovia, 8-9 November 2012.

Author

Borràs, Francesc E., Falcón-Pérez, Juan Manuel, Marcilla, Antonio, Mittelbrunn, María, del Portillo, Hernando A., Sánchez-Madrid, Francisco, and Yáñez-Mó, María

Subjects
VESICLES (Cytology), EXOSOMES, ORGANELLE formation, RNA, PARASITES, CONFERENCES & conventions
Abstract

The article discusses the highlights of the symposium of Grupo Español de Investigación en Vesículas Extracelulares (GEIVEX) held in Segovia, Spain on November 8-9, 2012. Issues covered include biogenesis of exosomes, RNA and extracellular vesicles and parasites and viral extracellular vesicles. Speakers at the event include clinicians Manuel Izquierdo, Miguel A. Alonso and Carolina Villarroya.

Published
2013
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16. The protein and microRNA cargo of extracellular vesicles from parasitic helminths – current status and research priorities.

Author

Sotillo, Javier, Robinson, Mark W., Kimber, Michael J., Cucher, Marcela, Ancarola, María Eugenia, Nejsum, Peter, Marcilla, Antonio, Eichenberger, Ramon M., and Tritten, Lucienne

Subjects
*EXTRACELLULAR vesicles, *HELMINTHS, *MICRORNA, *PROTEINS, *PLATYHELMINTHES, *MYOSIN
Abstract

• Protein and microRNA (miRNA) cargo data was compared across helminth groups. • EF-hand proteins are present in extracellular vesicles (EVs) from all platyhelminthes. • M13 metallopeptidases were common to EVs from all nematodes. • Nematodes shared two miRNA families, while five were found in all trematode EVs. • We discuss the heterogeneity of methods used for helminth EV isolation. Helminth parasites have a remarkable ability to persist within their mammalian hosts, which is largely due to their secretion of molecules with immunomodulatory properties. Although the soluble components of helminth secretions have been extensively studied, the discovery that helminths release extracellular vesicles (EVs) has added further complexity to the host-parasite interaction. Whilst several studies have begun to characterise the molecules carried by helminth EVs, work aimed at investigating their biological functions has been hindered by a lack of helminth-specific EV markers. To begin to address this, we summarised helminth EV literature to date. With a focus on the protein and microRNA (miRNA) cargo, we aimed to detect similarities and differences across those major groups of helminths for which data are available; namely nematodes, trematodes and cestodes. Pfam analysis revealed that although there is no universal EV marker for all helminth species, the EF-hand protein family was present in all EV datasets from cestodes and trematodes, and could serve as a platyhelminth EV biomarker. In contrast, M13 metallopeptidases and actin may have potential as markers for nematode EVs. As with proteins, many miRNA families appeared to be species-, stage-, or dataset-specific. Two miRNA families were common to nematode EVs (mir-10 and let-7); the miRNA cargo of EVs secreted by clade I species appeared somewhat different from species from other clades. Five miRNA families (mir-71, mir-10, mir-190, let-7 and mir-2) were shared by all trematode species examined. Our analysis has identified novel markers that may be used in studies aimed at characterising helminth EVs and interrogating their function at the host-parasite interface. In addition, we discuss the heterogeneity of methods used for helminth EV isolation and emphasise the need for a standardised approach in reporting on helminth EV data. [ABSTRACT FROM AUTHOR]

Published
2020
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17. Reprint of “EXOSOME LEVELS IN HUMAN BODY FLUIDS: A TUMOR MARKER BY THEMSELVES?”.

Author

Cappello, Francesco, Logozzi, Mariantonia, Campanella, Claudia, Bavisotto, Celeste Caruso, Marcilla, Antonio, Properzi, Francesca, and Fais, Stefano

Subjects
*EXOSOMES, *BODY fluids, *TUMOR markers, *VESICLES (Cytology), *EARLY detection of cancer
Abstract

Despite considerable research efforts, the finding of reliable tumor biomarkers remains challenging and unresolved. In recent years a novel diagnostic biomedical tool with high potential has been identified in extracellular nanovesicles or exosomes. They are released by the majority of the cells and contain detailed molecular information on the cell of origin including tumor hallmarks. Exosomes can be isolated from easy accessible body fluids, and most importantly, they can at once provide with several biomarkers, with different levels of specificity. Recent clinical evidence shows that the levels of exosomes released into body fluids may by themselves represent a predictive/diagnostic of tumors, discriminating cancer patients from healthy subjects. The aim of this review is to highlight these latest challenging findings to provide novel and groundbreaking ideas for successful tumor early diagnosis and follow-up. [ABSTRACT FROM AUTHOR]

Published
2017
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