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

Author

Welsh, Joshua, Goberdhan, Deborah, ODriscoll, Lorraine, Buzas, Edit, Blenkiron, Cherie, Bussolati, Benedetta, Cai, Houjian, Di Vizio, Dolores, Driedonks, Tom, Erdbrügger, Uta, Falcon-Perez, Juan, Fu, Qing-Ling, Hill, Andrew, Lenassi, Metka, Lim, Sai, Mahoney, Mỹ, Mohanty, Sujata, Möller, Andreas, Nieuwland, Rienk, Ochiya, Takahiro, Sahoo, Susmita, Torrecilhas, Ana, Zheng, Lei, Zijlstra, Andries, Abuelreich, Sarah, Bagabas, Reem, Bergese, Paolo, Bridges, Esther, Brucale, Marco, Burger, Dylan, Carney, Randy, Cocucci, Emanuele, Colombo, Federico, Crescitelli, Rossella, Hanser, Edveena, Harris, Adrian, Haughey, Norman, Hendrix, An, Ivanov, Alexander, Jovanovic-Talisman, Tijana, Kruh-Garcia, Nicole, Kuulei-Lyn Faustino, Vroniqa, Kyburz, Diego, Lässer, Cecilia, Lennon, Kathleen, Lötvall, Jan, Maddox, Adam, Martens-Uzunova, Elena, Mizenko, Rachel, Newman, Lauren, Ridolfi, Andrea, Rohde, Eva, Rojalin, Tatu, Rowland, Andrew, Saftics, Andras, Sandau, Ursula, Saugstad, Julie, Shekari, Faezeh, Swift, Simon, Ter-Ovanesyan, Dmitry, Tosar, Juan, Useckaite, Zivile, Valle, Francesco, Varga, Zoltan, van der Pol, Edwin, van Herwijnen, Martijn, Wauben, Marca, Wehman, Ann, Williams, Sarah, Zendrini, Andrea, Zimmerman, Alan, Théry, Clotilde, and Witwer, Kenneth

Subjects
MISEV, ectosomes, exosomes, extracellular particles, extracellular vesicles, guidelines, microparticles, microvesicles, minimal information requirements, reproducibility, rigor, standardisation, Extracellular Vesicles, Exosomes, Biological Transport, Biomarkers, Phenotype
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.

Published
2024

10. Extending gene ontology in the context of extracellular RNA and vesicle communication

Author

Cheung, Kei-Hoi, Keerthikumar, Shivakumar, Roncaglia, Paola, Subramanian, Sai Lakshmi, Roth, Matthew E, Samuel, Monisha, Anand, Sushma, Gangoda, Lahiru, Gould, Stephen, Alexander, Roger, Galas, David, Gerstein, Mark B, Hill, Andrew F, Kitchen, Robert R, Lötvall, Jan, Patel, Tushar, Procaccini, Dena C, Quesenberry, Peter, Rozowsky, Joel, Raffai, Robert L, Shypitsyna, Aleksandra, Su, Andrew I, Théry, Clotilde, Vickers, Kasey, Wauben, Marca HM, Mathivanan, Suresh, Milosavljevic, Aleksandar, and Laurent, Louise C

Subjects
Information and Computing Sciences, Genetics, Databases, Genetic, Extracellular Vesicles, Gene Ontology, Humans, Molecular Sequence Annotation, RNA, Web Browser, Ontology, Extracellular RNA, Extracellular vesicle, Metadata, Faceted search, Atlas, Other Biological Sciences, Artificial Intelligence and Image Processing, Information Systems, Information and computing sciences
Abstract

BackgroundTo address the lack of standard terminology to describe extracellular RNA (exRNA) data/metadata, we have launched an inter-community effort to extend the Gene Ontology (GO) with subcellular structure concepts relevant to the exRNA domain. By extending GO in this manner, the exRNA data/metadata will be more easily annotated and queried because it will be based on a shared set of terms and relationships relevant to extracellular research.MethodsBy following a consensus-building process, we have worked with several academic societies/consortia, including ERCC, ISEV, and ASEMV, to identify and approve a set of exRNA and extracellular vesicle-related terms and relationships that have been incorporated into GO. In addition, we have initiated an ongoing process of extractions of gene product annotations associated with these terms from Vesiclepedia and ExoCarta, conversion of the extracted annotations to Gene Association File (GAF) format for batch submission to GO, and curation of the submitted annotations by the GO Consortium. As a use case, we have incorporated some of the GO terms into annotations of samples from the exRNA Atlas and implemented a faceted search interface based on such annotations.ResultsWe have added 7 new terms and modified 9 existing terms (along with their synonyms and relationships) to GO. Additionally, 18,695 unique coding gene products (mRNAs and proteins) and 963 unique non-coding gene products (ncRNAs) which are associated with the terms: "extracellular vesicle", "extracellular exosome", "apoptotic body", and "microvesicle" were extracted from ExoCarta and Vesiclepedia. These annotations are currently being processed for submission to GO.ConclusionsAs an inter-community effort, we have made a substantial update to GO in the exRNA context. We have also demonstrated the utility of some of the new GO terms for sample annotation and metadata search.

Published
2016

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

Author

Welsh, Joshua A., Goberdhan, Deborah C. I., O’Driscoll, Lorraine, Buzas, Edit I., Blenkiron, Cherie, Bussolati, Benedetta, Cai, Houjian, Di Vizio, Dolores, Driedonks, Tom A. P., Erdbrügger, Uta, Falcon-Perez, Juan M., Fu, Qing-Ling, Hill, Andrew F., Lenassi, Metka, Lim, Sai Kiang, M˜y, G. Mahoney, Mohanty, Sujata, Möller, Andreas, Nieuwland, Rienk, Ochiya, Takahiro, Sahoo, Susmita, Torrecilhas, Ana C., Zheng, Lei, Zijlstra, Andries, Abuelreich, Sarah, Bagabas, Reem, Bergese, Paolo, Bridges, Esther M., Brucale, Marco, Burger, Dylan, Carney, Randy P., Cocucci, Emanuele, Crescitelli, Rossella, Hanser, Edveena, Harris, Adrian L., Haughey, Norman J., Hendrix, An, Ivanov, Alexander R., Jovanovic-Talisman, Tijana, Kruh-Garcia, Nicole A., Faustino, Vroniqa Ku’ulei-Lyn, Kyburz, Diego, Lässer, Cecilia, Lennon, Kathleen M., Lötvall, Jan, Maddox, Adam L., Martens-Uzunova, Elena S., Mizenko, Rachel R., Newman, Lauren A., Ridolfi, Andrea, Rohde, Eva, Rojalin, Tatu, Rowland, Andrew, Saftics, Andras, Sandau, Ursula S., Saugstad, Julie A., Shekari, Faezeh, Swift, Simon, Ter-Ovanesyan, Dmitry, Tosar, Juan P., Useckaite, Zivile, Valle, Francesco, Varga, Zoltan, van der Pol, Edwin, van Herwijnen, Martijn J. C., Wauben, Marca H. M., Wehman, Ann M., Williams, Sarah, Zendrini, Andrea, Zimmerman, Alan J., MISEV Consortium, Thery, Clotilde, Witwer, Kenneth W., Welsh, Joshua A., Goberdhan, Deborah C. I., O’Driscoll, Lorraine, Buzas, Edit I., Blenkiron, Cherie, Bussolati, Benedetta, Cai, Houjian, Di Vizio, Dolores, Driedonks, Tom A. P., Erdbrügger, Uta, Falcon-Perez, Juan M., Fu, Qing-Ling, Hill, Andrew F., Lenassi, Metka, Lim, Sai Kiang, M˜y, G. Mahoney, Mohanty, Sujata, Möller, Andreas, Nieuwland, Rienk, Ochiya, Takahiro, Sahoo, Susmita, Torrecilhas, Ana C., Zheng, Lei, Zijlstra, Andries, Abuelreich, Sarah, Bagabas, Reem, Bergese, Paolo, Bridges, Esther M., Brucale, Marco, Burger, Dylan, Carney, Randy P., Cocucci, Emanuele, Crescitelli, Rossella, Hanser, Edveena, Harris, Adrian L., Haughey, Norman J., Hendrix, An, Ivanov, Alexander R., Jovanovic-Talisman, Tijana, Kruh-Garcia, Nicole A., Faustino, Vroniqa Ku’ulei-Lyn, Kyburz, Diego, Lässer, Cecilia, Lennon, Kathleen M., Lötvall, Jan, Maddox, Adam L., Martens-Uzunova, Elena S., Mizenko, Rachel R., Newman, Lauren A., Ridolfi, Andrea, Rohde, Eva, Rojalin, Tatu, Rowland, Andrew, Saftics, Andras, Sandau, Ursula S., Saugstad, Julie A., Shekari, Faezeh, Swift, Simon, Ter-Ovanesyan, Dmitry, Tosar, Juan P., Useckaite, Zivile, Valle, Francesco, Varga, Zoltan, van der Pol, Edwin, van Herwijnen, Martijn J. C., Wauben, Marca H. M., Wehman, Ann M., Williams, Sarah, Zendrini, Andrea, Zimmerman, Alan J., MISEV Consortium, Thery, Clotilde, and Witwer, Kenneth W.

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., Godkänd;2024;Nivå 0;2024-04-05 (marisr);Full text license: CC BY

Published
2024
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12. Synovial fluid extracellular vesicles as arthritis biomarkers: the added value of lipid-profiling and integrated omics

Author

Varela, Laura, van de Lest, Chris H.A., René van Weeren, P., Wauben, Marca H.M., Varela, Laura, van de Lest, Chris H.A., René van Weeren, P., and Wauben, Marca H.M.

Abstract

Arthritis, a diverse group of inflammatory joint disorders, poses great challenges in early diagnosis and targeted treatment. Timely intervention is imperative, yet conventional diagnostic methods are not able to detect subtle early symptoms. Hence, there is an urgent need for specific biomarkers that discriminate between different arthritis forms and for early diagnosis. The pursuit of such precise diagnostic tools has prompted a growing interest in extracellular vesicles (EVs). EVs, released by cells in a regulated fashion, are detectable in body fluids, including synovial fluid (SF), which fills the joint space. They provide insights into the intricate molecular landscapes of arthritis, and this has stimulated the search for minimally invasive EV-based diagnostics. As such, the analysis of EVs in SF has become a focus for identifying EV-based biomarkers for joint disease endotyping, prognosis, and progression. EVs are composed of a lipid bilayer and a wide variety of different cargo types, of which proteins and RNAs are widely investigated. In contrast, membrane lipids of EVs, especially the abundance, presence, or absence of specific lipids and their contribution to the biological activity of EVs, are largely overlooked in EV research. Furthermore, the identification of specific combinations of different EV components acting in concert in EVs can fuel the definition of composite biomarkers. We here provide a state-of-the-art overview of the knowledge on SF-derived EVs with emphasis on lipid analysis and we give an example of the added value of integrated proteomics and lipidomics analysis in the search for composite EV-associated biomarkers.

Published
2024

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

Author

Welsh, Joshua A, Goberdhan, Deborah C I, O'Driscoll, Lorraine, Buzas, Edit I, Blenkiron, Cherie, Bussolati, Benedetta, Cai, Houjian, Di Vizio, Dolores, Driedonks, Tom A P, Erdbrügger, Uta, Falcon-Perez, Juan M, Fu, Qing-Ling, Hill, Andrew F, Lenassi, Metka, Lim, Sai Kiang, Mahoney, Mỹ G, Mohanty, Sujata, Möller, Andreas, Nieuwland, Rienk, Ochiya, Takahiro, Sahoo, Susmita, Torrecilhas, Ana C, Zheng, Lei, Zijlstra, Andries, Abuelreich, Sarah, Bagabas, Reem, Bergese, Paolo, Bridges, Esther M, Brucale, Marco, Burger, Dylan, Carney, Randy P, Cocucci, Emanuele, Colombo, Federico, Crescitelli, Rossella, Hanser, Edveena, Harris, Adrian L, Haughey, Norman J, Hendrix, An, Ivanov, Alexander R, Jovanovic-Talisman, Tijana, Kruh-Garcia, Nicole A, Ku'ulei-Lyn Faustino, Vroniqa, Kyburz, Diego, Lässer, Cecilia, Lennon, Kathleen M, Lötvall, Jan, Maddox, Adam L, Martens-Uzunova, Elena S, Mizenko, Rachel R, Newman, Lauren A, Ridolfi, Andrea, Rohde, Eva, Rojalin, Tatu, Rowland, Andrew, Saftics, Andras, Sandau, Ursula S, Saugstad, Julie A, Shekari, Faezeh, Swift, Simon, Ter-Ovanesyan, Dmitry, Tosar, Juan P, Useckaite, Zivile, Valle, Francesco, Varga, Zoltan, van der Pol, Edwin, van Herwijnen, Martijn J C, Wauben, Marca H M, Wehman, Ann M, Williams, Sarah, Zendrini, Andrea, Zimmerman, Alan J, Misev Consortium, null, Théry, Clotilde, Witwer, Kenneth W, Stoorvogel, Willem, Welsh, Joshua A, Goberdhan, Deborah C I, O'Driscoll, Lorraine, Buzas, Edit I, Blenkiron, Cherie, Bussolati, Benedetta, Cai, Houjian, Di Vizio, Dolores, Driedonks, Tom A P, Erdbrügger, Uta, Falcon-Perez, Juan M, Fu, Qing-Ling, Hill, Andrew F, Lenassi, Metka, Lim, Sai Kiang, Mahoney, Mỹ G, Mohanty, Sujata, Möller, Andreas, Nieuwland, Rienk, Ochiya, Takahiro, Sahoo, Susmita, Torrecilhas, Ana C, Zheng, Lei, Zijlstra, Andries, Abuelreich, Sarah, Bagabas, Reem, Bergese, Paolo, Bridges, Esther M, Brucale, Marco, Burger, Dylan, Carney, Randy P, Cocucci, Emanuele, Colombo, Federico, Crescitelli, Rossella, Hanser, Edveena, Harris, Adrian L, Haughey, Norman J, Hendrix, An, Ivanov, Alexander R, Jovanovic-Talisman, Tijana, Kruh-Garcia, Nicole A, Ku'ulei-Lyn Faustino, Vroniqa, Kyburz, Diego, Lässer, Cecilia, Lennon, Kathleen M, Lötvall, Jan, Maddox, Adam L, Martens-Uzunova, Elena S, Mizenko, Rachel R, Newman, Lauren A, Ridolfi, Andrea, Rohde, Eva, Rojalin, Tatu, Rowland, Andrew, Saftics, Andras, Sandau, Ursula S, Saugstad, Julie A, Shekari, Faezeh, Swift, Simon, Ter-Ovanesyan, Dmitry, Tosar, Juan P, Useckaite, Zivile, Valle, Francesco, Varga, Zoltan, van der Pol, Edwin, van Herwijnen, Martijn J C, Wauben, Marca H M, Wehman, Ann M, Williams, Sarah, Zendrini, Andrea, Zimmerman, Alan J, Misev Consortium, null, Théry, Clotilde, Witwer, Kenneth W, and Stoorvogel, Willem

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.

Published
2024

14. GABARAPL1 is essential in extracellular vesicle cargo loading and metastasis development

Author

Beaumont, Joel E J, Ju, Jinzhe, Barbeau, Lydie M O, Demers, Imke, Savelkouls, Kim G, Derks, Kasper, Bouwman, Freek G, Wauben, Marca H M, Zonneveld, Marijke I, Keulers, Tom G H, Rouschop, Kasper M A, Beaumont, Joel E J, Ju, Jinzhe, Barbeau, Lydie M O, Demers, Imke, Savelkouls, Kim G, Derks, Kasper, Bouwman, Freek G, Wauben, Marca H M, Zonneveld, Marijke I, Keulers, Tom G H, and Rouschop, Kasper M A

Abstract

Background and purpose: Hypoxia is a common feature of tumours, associated with poor prognosis due to increased resistance to radio- and chemotherapy and enhanced metastasis development. Previously we demonstrated that GABARAPL1 is required for the secretion of extracellular vesicles (EV) with pro-angiogenic properties during hypoxia. Here, we explored the role of GABARAPL1+ EV in the metastatic cascade. Materials and methods: GABARAPL1 deficient or control MDA-MB-231 cells were injected in murine mammary fat pads. Lungs were dissected and analysed for human cytokeratin 18. EV from control and GABARAPL1 deficient cells exposed to normoxia (21% O2) or hypoxia (O2 < 0.02%) were isolated and analysed by immunoblot, nanoparticle tracking analysis, high resolution flow cytometry, mass spectrometry and next-generation sequencing. Cellular migration and invasion were analysed using scratch assays and transwell-invasion assays, respectively. Results: The number of pulmonary metastases derived from GABARAPL1 deficient tumours decreased by 84%. GABARAPL1 deficient cells migrate slower but display a comparable invasive capacity. Both normoxic and hypoxic EV contain proteins and miRNAs associated with metastasis development and, in line, increase cancer cell invasiveness. Although GABARAPL1 deficiency alters EV content, it does not alter the EV-induced increase in cancer cell invasiveness. Conclusion: GABARAPL1 is essential for metastasis development. This is unrelated to changes in migration and invasion and suggests that GABARAPL1 or GABARAPL1+ EV are essential in other processes related to the metastatic cascade.

Published
2024

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

Author

Celbiologie, Cell Biology, Metabolism & Cancer - Cellbiology, Welsh, Joshua A, Goberdhan, Deborah C I, O'Driscoll, Lorraine, Buzas, Edit I, Blenkiron, Cherie, Bussolati, Benedetta, Cai, Houjian, Di Vizio, Dolores, Driedonks, Tom A P, Erdbrügger, Uta, Falcon-Perez, Juan M, Fu, Qing-Ling, Hill, Andrew F, Lenassi, Metka, Lim, Sai Kiang, Mahoney, Mỹ G, Mohanty, Sujata, Möller, Andreas, Nieuwland, Rienk, Ochiya, Takahiro, Sahoo, Susmita, Torrecilhas, Ana C, Zheng, Lei, Zijlstra, Andries, Abuelreich, Sarah, Bagabas, Reem, Bergese, Paolo, Bridges, Esther M, Brucale, Marco, Burger, Dylan, Carney, Randy P, Cocucci, Emanuele, Colombo, Federico, Crescitelli, Rossella, Hanser, Edveena, Harris, Adrian L, Haughey, Norman J, Hendrix, An, Ivanov, Alexander R, Jovanovic-Talisman, Tijana, Kruh-Garcia, Nicole A, Ku'ulei-Lyn Faustino, Vroniqa, Kyburz, Diego, Lässer, Cecilia, Lennon, Kathleen M, Lötvall, Jan, Maddox, Adam L, Martens-Uzunova, Elena S, Mizenko, Rachel R, Newman, Lauren A, Ridolfi, Andrea, Rohde, Eva, Rojalin, Tatu, Rowland, Andrew, Saftics, Andras, Sandau, Ursula S, Saugstad, Julie A, Shekari, Faezeh, Swift, Simon, Ter-Ovanesyan, Dmitry, Tosar, Juan P, Useckaite, Zivile, Valle, Francesco, Varga, Zoltan, van der Pol, Edwin, van Herwijnen, Martijn J C, Wauben, Marca H M, Wehman, Ann M, Williams, Sarah, Zendrini, Andrea, Zimmerman, Alan J, Misev Consortium, Théry, Clotilde, Witwer, Kenneth W, Stoorvogel, Willem, Celbiologie, Cell Biology, Metabolism & Cancer - Cellbiology, Welsh, Joshua A, Goberdhan, Deborah C I, O'Driscoll, Lorraine, Buzas, Edit I, Blenkiron, Cherie, Bussolati, Benedetta, Cai, Houjian, Di Vizio, Dolores, Driedonks, Tom A P, Erdbrügger, Uta, Falcon-Perez, Juan M, Fu, Qing-Ling, Hill, Andrew F, Lenassi, Metka, Lim, Sai Kiang, Mahoney, Mỹ G, Mohanty, Sujata, Möller, Andreas, Nieuwland, Rienk, Ochiya, Takahiro, Sahoo, Susmita, Torrecilhas, Ana C, Zheng, Lei, Zijlstra, Andries, Abuelreich, Sarah, Bagabas, Reem, Bergese, Paolo, Bridges, Esther M, Brucale, Marco, Burger, Dylan, Carney, Randy P, Cocucci, Emanuele, Colombo, Federico, Crescitelli, Rossella, Hanser, Edveena, Harris, Adrian L, Haughey, Norman J, Hendrix, An, Ivanov, Alexander R, Jovanovic-Talisman, Tijana, Kruh-Garcia, Nicole A, Ku'ulei-Lyn Faustino, Vroniqa, Kyburz, Diego, Lässer, Cecilia, Lennon, Kathleen M, Lötvall, Jan, Maddox, Adam L, Martens-Uzunova, Elena S, Mizenko, Rachel R, Newman, Lauren A, Ridolfi, Andrea, Rohde, Eva, Rojalin, Tatu, Rowland, Andrew, Saftics, Andras, Sandau, Ursula S, Saugstad, Julie A, Shekari, Faezeh, Swift, Simon, Ter-Ovanesyan, Dmitry, Tosar, Juan P, Useckaite, Zivile, Valle, Francesco, Varga, Zoltan, van der Pol, Edwin, van Herwijnen, Martijn J C, Wauben, Marca H M, Wehman, Ann M, Williams, Sarah, Zendrini, Andrea, Zimmerman, Alan J, Misev Consortium, Théry, Clotilde, Witwer, Kenneth W, and Stoorvogel, Willem

Published
2024

16. Proteome and phospholipidome interrelationship of synovial fluid-derived extracellular vesicles in equine osteoarthritis: An exploratory 'multi-omics' study to identify composite biomarkers

Author

IOV Facs, Dep Clinical Sciences, Equine Musculoskeletal Biology, CS_Locomotion, Veterinaire biochemie, Celbiologie, Cell Biology, Metabolism & Cancer - Cellbiology, Cell Biology, Metabolism & Cancer - Metabolomics, Research Department OH - Biomolecular Health Sciences, Locomotion - Equine Sciences, Clarke, Emily, Varela, Laura, Jenkins, Rosalind E, Lozano-Andrés, Estefanía, Cywińska, Anna, Przewozny, Maciej, van Weeren, P René, van de Lest, Chris H A, Peffers, Mandy, Wauben, Marca H M, IOV Facs, Dep Clinical Sciences, Equine Musculoskeletal Biology, CS_Locomotion, Veterinaire biochemie, Celbiologie, Cell Biology, Metabolism & Cancer - Cellbiology, Cell Biology, Metabolism & Cancer - Metabolomics, Research Department OH - Biomolecular Health Sciences, Locomotion - Equine Sciences, Clarke, Emily, Varela, Laura, Jenkins, Rosalind E, Lozano-Andrés, Estefanía, Cywińska, Anna, Przewozny, Maciej, van Weeren, P René, van de Lest, Chris H A, Peffers, Mandy, and Wauben, Marca H M

Published
2024

17. Intrinsic variability of fluorescence calibrators impacts the assignment of MESF or ERF values to nanoparticles and extracellular vesicles by flow cytometry

Author

IOV Facs, Celbiologie, Cell Biology, Metabolism & Cancer - Cellbiology, Research Department OH - Biomolecular Health Sciences, Lozano-Andrés, Estefanía, Van Den Broeck, Tina, Wang, Lili, Mehrpouyan, Majid, Tian, Ye, Yan, Xiaomei, Arkesteijn, Ger J A, Wauben, Marca H M, IOV Facs, Celbiologie, Cell Biology, Metabolism & Cancer - Cellbiology, Research Department OH - Biomolecular Health Sciences, Lozano-Andrés, Estefanía, Van Den Broeck, Tina, Wang, Lili, Mehrpouyan, Majid, Tian, Ye, Yan, Xiaomei, Arkesteijn, Ger J A, and Wauben, Marca H M

Published
2024

18. GABARAPL1 is essential in extracellular vesicle cargo loading and metastasis development

Author

Celbiologie, Cell Biology, Metabolism & Cancer - Cellbiology, Beaumont, Joel E J, Ju, Jinzhe, Barbeau, Lydie M O, Demers, Imke, Savelkouls, Kim G, Derks, Kasper, Bouwman, Freek G, Wauben, Marca H M, Zonneveld, Marijke I, Keulers, Tom G H, Rouschop, Kasper M A, Celbiologie, Cell Biology, Metabolism & Cancer - Cellbiology, Beaumont, Joel E J, Ju, Jinzhe, Barbeau, Lydie M O, Demers, Imke, Savelkouls, Kim G, Derks, Kasper, Bouwman, Freek G, Wauben, Marca H M, Zonneveld, Marijke I, Keulers, Tom G H, and Rouschop, Kasper M A

Published
2024

19. Obstacles and opportunities in the functional analysis of extracellular vesicle RNA – an ISEV position paper

Author

Mateescu, Bogdan, Kowal, Emma J. K., Van Balkom, Bas W. M. Emma J. K., Bartel, Sabine, Bhattacharyya, Suvendra N., Buzás, Edit I., Buck, Amy H., Candia, Paola de, Chow, Franklin W. N., Das, Saumya, Driedonks, Tom A. P., Fernández Messina, Lola María, Haderk, Franziska, Hill, Andrew F., Jones, Jennifer C., Van Keuren‐Jensen, Kendall R., Lai, Charles P., Lässer, Cecilia, di Liegro, Italia, Lunavat, Taral R., Lorenowicz, Magdalena J., Maas, Sybren L. N., Mäger, Imre, Mittelbrunn, Maria, Momma, Stefan, Mukherjee, Kamalika, Nawaz, Muhammad, Pegtel, D. Michiel, Pfaffl, Michael W., Schiffelers, Raymond M., Tahara, Hidetoshi, Théry, Clotilde, Tosar, Juan Pablo, Wauben, Marca H. M., Witwer, Kenneth W., Nolte‐'t Hoen, Esther N. M., Mateescu, Bogdan, Kowal, Emma J. K., Van Balkom, Bas W. M. Emma J. K., Bartel, Sabine, Bhattacharyya, Suvendra N., Buzás, Edit I., Buck, Amy H., Candia, Paola de, Chow, Franklin W. N., Das, Saumya, Driedonks, Tom A. P., Fernández Messina, Lola María, Haderk, Franziska, Hill, Andrew F., Jones, Jennifer C., Van Keuren‐Jensen, Kendall R., Lai, Charles P., Lässer, Cecilia, di Liegro, Italia, Lunavat, Taral R., Lorenowicz, Magdalena J., Maas, Sybren L. N., Mäger, Imre, Mittelbrunn, Maria, Momma, Stefan, Mukherjee, Kamalika, Nawaz, Muhammad, Pegtel, D. Michiel, Pfaffl, Michael W., Schiffelers, Raymond M., Tahara, Hidetoshi, Théry, Clotilde, Tosar, Juan Pablo, Wauben, Marca H. M., Witwer, Kenneth W., and Nolte‐'t Hoen, Esther N. M.

Abstract

Acknowledgements We thank all participants of the 2015 ISEV workshop on EV-RNA for their valuable input in roundtable discussions, which formed the basis for this position paper. We are grateful to Dr P. Vader for preparing Figure 3., The release of RNA-containing extracellular vesicles (EV) into the extracellular milieu has been demonstrated in a multitude of different in vitro cell systems and in a variety of body fluids. RNA-containing EV are in the limelight for their capacity to communicate genetically encoded messages to other cells, their suitability as candidate biomarkers for diseases, and their use as therapeutic agents. Although EV-RNA has attracted enormous interest from basic researchers, clinicians, and industry, we currently have limited knowledge on which mechanisms drive and regulate RNA incorporation into EV and on how RNA-encoded messages affect signalling processes in EV-targeted cells. Moreover, EV-RNA research faces various technical challenges, such as standardisation of EV isolation methods, optimisation of methodologies to isolate and characterise minute quantities of RNA found in EV, and development of approaches to demonstrate functional transfer of EV-RNA in vivo. These topics were discussed at the 2015 EV-RNA workshop of the International Society for Extracellular Vesicles. This position paper was written by the participants of the workshop not only to give an overview of the current state of knowledge in the field, but also to clarify that our incomplete knowledge – of the nature of EV(-RNA)s and of how to effectively and reliably study them – currently prohibits the implementation of gold standards in EV-RNA research. In addition, this paper creates awareness of possibilities and limitations of currently used strategies to investigate EV-RNA and calls for caution in interpretation of the obtained data., Depto. de Biología Celular, Fac. de Ciencias Biológicas, TRUE, pub

Published
2024

20. Lipidome profiling of human and equine neutrophil-derived extracellular vesicles and their potential contribution to the ensemble of synovial fluid-derived extracellular vesicles during joint inflammation

Author

Varela, Laura, primary, Mol, Sanne, additional, Taanman-Kueter, Esther W., additional, Ryan, Sarah E., additional, Taams, Leonie S., additional, de Jong, Esther, additional, van Weeren, P. René, additional, van de Lest, Chris H.A., additional, and Wauben, Marca H.M., additional

Published
2023
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21. Physical association of low density lipoprotein particles and extracellular vesicles unveiled by single particle analysis

Author

Lozano‐Andrés, Estefanía, primary, Enciso‐Martinez, Agustin, additional, Gijsbers, Abril, additional, Ridolfi, Andrea, additional, Van Niel, Guillaume, additional, Libregts, Sten F. W. M., additional, Pinheiro, Cláudio, additional, van Herwijnen, Martijn J. C., additional, Hendrix, An, additional, Brucale, Marco, additional, Valle, Francesco, additional, Peters, Peter J., additional, Otto, Cees, additional, Arkesteijn, Ger J. A., additional, and Wauben, Marca H. M., additional

Published
2023
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26. Maternal allergic sensitization affects the T cell modulatory capacity and molecular cargo of milk derived extracellular vesicles

Author

van Herwijnen, Martijn J. C., primary, Giovanazzi, Alberta, additional, Zonneveld, Marijke I., additional, Maqueda, Joaquin J., additional, Kleinjan, Marije, additional, Goerdayal, Soenita, additional, Vollmy, Franziska, additional, van Bruggen - de Haan, Arianne, additional, Driedonks, Tom A.P., additional, Arkesteijn, Ger J.A., additional, van Elburg, Ruurd M., additional, van der Meulen, Gerbrich N., additional, Garssen, Johan, additional, Oliveira, Carla, additional, Altelaar, A.F. Maarten, additional, 't Hoen, Peter A.C., additional, Redegeld, Frank A., additional, Nolte- 't Hoen, Esther N.M., additional, and Wauben, Marca H.M., additional

Published
2023
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27. Proteome and phospholipidome interrelationship of synovial fluid-derived extracellular vesicles in equine osteoarthritis: An exploratory ‘multi-omics’ study to identify composite biomarkers

Author

Clarke, Emily J, primary, Varela, Laura, additional, Jenkins, Rosalind E, additional, Lozano−Andrés, Estefanía, additional, Cywińska, Anna, additional, Przewozny, Maciej, additional, van Weeren, P. René, additional, van de Lest, Chris H.A., additional, Peffers, Mandy, additional, and Wauben, Marca H.M., additional

Published
2023
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28. The generation and use of recombinant extracellular vesicles as biological reference material

Author

Geeurickx, Edward, Tulkens, Joeri, Dhondt, Bert, Van Deun, Jan, Lippens, Lien, Vergauwen, Glenn, Heyrman, Elisa, De Sutter, Delphine, Gevaert, Kris, Impens, Francis, Miinalainen, Ilkka, Van Bockstal, Pieter-Jan, De Beer, Thomas, Wauben, Marca H. M., Nolte-‘t-Hoen, Esther N. M., Bloch, Katarzyna, Swinnen, Johannes V., van der Pol, Edwin, Nieuwland, Rienk, Braems, Geert, Callewaert, Nico, Mestdagh, Pieter, Vandesompele, Jo, Denys, Hannelore, Eyckerman, Sven, De Wever, Olivier, and Hendrix, An

Published
2019
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33. Physical association of low density lipoprotein particles and extracellular vesicles unveiled by single particle analysis

Author

Lozano-Andrés, Estefanía, Enciso-Martinez, Agustin, Gijsbers, Abril, Ridolfi, Andrea, Van Niel, Guillaume, Libregts, Sten F W M, Pinheiro, Cláudio, van Herwijnen, Martijn J C, Hendrix, An, Brucale, Marco, Valle, Francesco, Peters, Peter J, Otto, Cees, Arkesteijn, Ger J A, Wauben, Marca H M, Lozano-Andrés, Estefanía, Enciso-Martinez, Agustin, Gijsbers, Abril, Ridolfi, Andrea, Van Niel, Guillaume, Libregts, Sten F W M, Pinheiro, Cláudio, van Herwijnen, Martijn J C, Hendrix, An, Brucale, Marco, Valle, Francesco, Peters, Peter J, Otto, Cees, Arkesteijn, Ger J A, and Wauben, Marca H M

Abstract

Extracellular vesicles (EVs) in blood plasma are recognized as potential biomarkers for disease. Although blood plasma is easily obtainable, analysis of EVs at the single particle level is still challenging due to the biological complexity of this body fluid. Besides EVs, plasma contains different types of lipoproteins particles (LPPs), that outnumber EVs by orders of magnitude and which partially overlap in biophysical properties such as size, density and molecular makeup. Consequently, during EV isolation LPPs are often co-isolated. Furthermore, physical EV-LPP complexes have been observed in purified EV preparations. Since co-isolation or association of LPPs can impact EV-based analysis and biomarker profiling, we investigated the presence and formation of EV-LPP complexes in biological samples by using label-free atomic force microscopy, cryo-electron tomography and synchronous Rayleigh and Raman scattering analysis of optically trapped particles and fluorescence-based high sensitivity single particle flow cytometry. Furthermore, we evaluated the impact on flow cytometric analysis in the presence of LPPs using in vitro spike-in experiments of purified tumour cell line-derived EVs in different classes of purified human LPPs. Based on orthogonal single-particle analysis techniques we demonstrate that EV-LPP complexes can form under physiological conditions. Furthermore, we show that in fluorescence-based flow cytometric EV analysis staining of LPPs, as well as EV-LPP associations, can influence quantitative and qualitative EV analysis. Lastly, we demonstrate that the colloidal matrix of the biofluid in which EVs reside impacts their buoyant density, size and/or refractive index (RI), which may have consequences for down-stream EV analysis and EV biomarker profiling.

Published
2023

34. A combined western and bead-based multiplex platform to characterize extracellular vesicles

Author

van Maanen, Josette, Bach, Frances C, Braun, Theresa S, Giovanazzi, Alberta, van Balkom, Bas W M, Templin, Markus, Wauben, Marca H M, Tryfonidou, Marianna A, van Maanen, Josette, Bach, Frances C, Braun, Theresa S, Giovanazzi, Alberta, van Balkom, Bas W M, Templin, Markus, Wauben, Marca H M, and Tryfonidou, Marianna A

Abstract

In regenerative medicine, extracellular vesicles (EVs) are considered as a promising cell-free approach. EVs are lipid bilayer-enclosed vesicles secreted by cells and are key players in intercellular communication. EV-based therapeutic approaches have unique advantages over the use of cell-based therapies, such as a high biological, but low immunogenic and tumorigenic potential. To analyze the purity and biochemical composition of EV preparations, the International Society for Extracellular Vesicles (ISEV) has prepared guidelines recommending the analysis of multiple (EV) markers, as well as proteins coisolated/recovered with EVs. Traditional methods for EV characterization, such as Western blotting, require a relatively high EV sample/protein input for the analysis of one protein. We here evaluate a combined Western and bead-based multiplex platform, called DigiWest, for its ability to detect simultaneously multiple EV markers in an EV-containing sample with inherent low protein input. DigiWest analysis was performed on EVs from various sources and species, including mesenchymal stromal cells, notochordal cells, and milk, from human, pig, and dog. The study established a panel of nine antibodies that can be used as cross-species for the detection of general EV markers and coisolates in accordance with the ISEV guidelines. This optimized panel facilitates the parallel evaluation of EV-containing samples, allowing for a comprehensive characterization and assessment of their purity. The total protein input for marker analysis with DigiWest was 1 mg for all nine antibodies, compared with *10 mg protein input required for traditional Western blotting for one antibody. These findings demonstrate the potential of the DigiWest technique for characterizing various types of EVs in the regenerative medicine field.

Published
2023

35. A compendium of single extracellular vesicle flow cytometry

Author

Welsh, Joshua A, Arkesteijn, Ger J A, Bremer, Michel, Cimorelli, Michael, Dignat-George, Françoise, Giebel, Bernd, Görgens, André, Hendrix, An, Kuiper, Martine, Lacroix, Romaric, Lannigan, Joanne, van Leeuwen, Ton G, Lozano-Andrés, Estefanía, Rao, Shoaib, Robert, Stéphane, de Rond, Leonie, Tang, Vera A, Tertel, Tobias, Yan, Xiaomei, Wauben, Marca H M, Nolan, John P, Jones, Jennifer C, Nieuwland, Rienk, van der Pol, Edwin, Welsh, Joshua A, Arkesteijn, Ger J A, Bremer, Michel, Cimorelli, Michael, Dignat-George, Françoise, Giebel, Bernd, Görgens, André, Hendrix, An, Kuiper, Martine, Lacroix, Romaric, Lannigan, Joanne, van Leeuwen, Ton G, Lozano-Andrés, Estefanía, Rao, Shoaib, Robert, Stéphane, de Rond, Leonie, Tang, Vera A, Tertel, Tobias, Yan, Xiaomei, Wauben, Marca H M, Nolan, John P, Jones, Jennifer C, Nieuwland, Rienk, and van der Pol, Edwin

Abstract

Flow cytometry (FCM) offers a multiparametric technology capable of characterizing single extracellular vesicles (EVs). However, most flow cytometers are designed to detect cells, which are larger than EVs. Whereas cells exceed the background noise, signals originating from EVs partly overlap with the background noise, thereby making EVs more difficult to detect than cells. This technical mismatch together with complexity of EV-containing fluids causes limitations and challenges with conducting, interpreting and reproducing EV FCM experiments. To address and overcome these challenges, researchers from the International Society for Extracellular Vesicles (ISEV), International Society for Advancement of Cytometry (ISAC), and the International Society on Thrombosis and Haemostasis (ISTH) joined forces and initiated the EV FCM working group. To improve the interpretation, reporting, and reproducibility of future EV FCM data, the EV FCM working group published an ISEV position manuscript outlining a framework of minimum information that should be reported about an FCM experiment on single EVs (MIFlowCyt-EV). However, the framework contains limited background information. Therefore, the goal of this compendium is to provide the background information necessary to design and conduct reproducible EV FCM experiments. This compendium contains background information on EVs, the interaction between light and EVs, FCM hardware, experimental design and preanalytical procedures, sample preparation, assay controls, instrument data acquisition and calibration, EV characterization, and data reporting. Although this compendium focuses on EVs, many concepts and explanations could also be applied to FCM detection of other particles within the EV size range, such as bacteria, lipoprotein particles, milk fat globules, and viruses.

Published
2023

36. Hyaluronic Acid in Synovial Fluid Prevents Neutrophil Activation in Spondyloarthritis

Author

Mol, Sanne, Taanman-Kueter, Esther W. M., Steen, Baltus A. van der, Kormelink, Tom Groot, Sande, Marleen G. H. van de, Tas, Sander, Wauben, Marca, Jong, Esther C. de, Mol, Sanne, Taanman-Kueter, Esther W. M., Steen, Baltus A. van der, Kormelink, Tom Groot, Sande, Marleen G. H. van de, Tas, Sander, Wauben, Marca, and Jong, Esther C. de

Abstract

Spondyloarthritis (SpA) patients suffer from joint inflammation resulting in tissue damage, characterized by the presence of numerous neutrophils in the synovium and synovial fluid (SF). As it is yet unclear to what extent neutrophils contribute to the pathogenesis of SpA, we set out to study SF neutrophils in more detail. We analyzed the functionality of SF neutrophils of 20 SpA patients and 7 disease controls, determining ROS production and degranulation in response to various stimuli. In addition, the effect of SF on neutrophil function was determined. Surprisingly, our data show that SF neutrophils in SpA patients have an inactive phenotype, despite the presence of many neutrophil-activating stimuli such as GM-CSF and TNF in SF. This was not due to exhaustion as SF neutrophils readily responded to stimulation. Therefore, this finding suggests that one or more inhibitors of neutrophil activation may be present in SF. Indeed, when blood neutrophils from healthy donors were activated in the presence of increasing concentrations of SF from SpA patients, degranulation and ROS production were dose-dependently inhibited. This effect was independent of diagnosis, gender, age, and medication in the patients from which the SF was isolated. Treatment of SF with the enzyme hyaluronidase strongly reduced the inhibitory effect of SF on neutrophil activation, indicating that hyaluronic acid that is present in SF may be an important factor in preventing SF neutrophil activation. This finding provides novel insights into the role of soluble factors in SF regulating neutrophil function and may lead to the development of novel therapeutics targeting neutrophil activation via hyaluronic acid or associated pathways.

Published
2023

37. Methods for the identification and characterization of extracellular vesicles in cardiovascular studies - from exosomes to microvesicles

Author

Davidson, Sean M, Boulanger, Chantal M, Aikawa, Elena, Badimon, Lina, Barile, Lucio, Binder, Christoph J, Brisson, Alain, Buzas, Edit, Emanueli, Costanza, Jansen, Felix, Katsur, Miroslava, Lacroix, Romaric, Lim, Sai Kiang, Mackman, Nigel, Mayr, Manuel, Menasché, Philippe, Nieuwland, Rienk, Sahoo, Susmita, Takov, Kaloyan, Thum, Thomas, Vader, Pieter, Wauben, Marca H M, Witwer, Kenneth, Sluijter, Joost P G, Davidson, Sean M, Boulanger, Chantal M, Aikawa, Elena, Badimon, Lina, Barile, Lucio, Binder, Christoph J, Brisson, Alain, Buzas, Edit, Emanueli, Costanza, Jansen, Felix, Katsur, Miroslava, Lacroix, Romaric, Lim, Sai Kiang, Mackman, Nigel, Mayr, Manuel, Menasché, Philippe, Nieuwland, Rienk, Sahoo, Susmita, Takov, Kaloyan, Thum, Thomas, Vader, Pieter, Wauben, Marca H M, Witwer, Kenneth, and Sluijter, Joost P G

Abstract

Extracellular vesicles (EVs) are nanosized vesicles with a lipid bilayer that are released from cells of the cardiovascular system, and are considered important mediators of intercellular and extracellular communications. Two types of EVs of particular interest are exosomes and microvesicles, which have been identified in all tissue and body fluids and carry a variety of molecules including RNAs, proteins, and lipids. EVs have potential for use in the diagnosis and prognosis of cardiovascular diseases and as new therapeutic agents, particularly in the setting of myocardial infarction and heart failure. Despite their promise, technical challenges related to their small size make it challenging to accurately identify and characterize them, and to study EV-mediated processes. Here, we aim to provide the reader with an overview of the techniques and technologies available for the separation and characterization of EVs from different sources. Methods for determining the protein, RNA, and lipid content of EVs are discussed. The aim of this document is to provide guidance on critical methodological issues and highlight key points for consideration for the investigation of EVs in cardiovascular studies.

Published
2023

39. Electrostatic interactions control the adsorption of extracellular vesicles onto supported lipid bilayers

Author

Celbiologie, Ridolfi, Andrea, Cardellini, Jacopo, Gashi, Fatlinda, Herwijnen, Martijn J.C. van, Trulsson, Martin, Campos-Terán, José, Wauben, Marca H. M., Berti, Debora, Nylander, Tommy, Stenhammar, Joakim, Celbiologie, Ridolfi, Andrea, Cardellini, Jacopo, Gashi, Fatlinda, Herwijnen, Martijn J.C. van, Trulsson, Martin, Campos-Terán, José, Wauben, Marca H. M., Berti, Debora, Nylander, Tommy, and Stenhammar, Joakim

Published
2023

42. Hyaluronic Acid in Synovial Fluid Prevents Neutrophil Activation in Spondyloarthritis

Author

Celbiologie, Mol, Sanne, Taanman-Kueter, Esther W. M., Steen, Baltus A. van der, Kormelink, Tom Groot, Sande, Marleen G. H. van de, Tas, Sander, Wauben, Marca, Jong, Esther C. de, Celbiologie, Mol, Sanne, Taanman-Kueter, Esther W. M., Steen, Baltus A. van der, Kormelink, Tom Groot, Sande, Marleen G. H. van de, Tas, Sander, Wauben, Marca, and Jong, Esther C. de

Published
2023

43. A compendium of single extracellular vesicle flow cytometry

Author

IOV Facs, Celbiologie, Welsh, Joshua A, Arkesteijn, Ger J A, Bremer, Michel, Cimorelli, Michael, Dignat-George, Françoise, Giebel, Bernd, Görgens, André, Hendrix, An, Kuiper, Martine, Lacroix, Romaric, Lannigan, Joanne, van Leeuwen, Ton G, Lozano-Andrés, Estefanía, Rao, Shoaib, Robert, Stéphane, de Rond, Leonie, Tang, Vera A, Tertel, Tobias, Yan, Xiaomei, Wauben, Marca H M, Nolan, John P, Jones, Jennifer C, Nieuwland, Rienk, van der Pol, Edwin, IOV Facs, Celbiologie, Welsh, Joshua A, Arkesteijn, Ger J A, Bremer, Michel, Cimorelli, Michael, Dignat-George, Françoise, Giebel, Bernd, Görgens, André, Hendrix, An, Kuiper, Martine, Lacroix, Romaric, Lannigan, Joanne, van Leeuwen, Ton G, Lozano-Andrés, Estefanía, Rao, Shoaib, Robert, Stéphane, de Rond, Leonie, Tang, Vera A, Tertel, Tobias, Yan, Xiaomei, Wauben, Marca H M, Nolan, John P, Jones, Jennifer C, Nieuwland, Rienk, and van der Pol, Edwin

Published
2023

44. Physical association of low density lipoprotein particles and extracellular vesicles unveiled by single particle analysis

Author

IOV Facs, Celbiologie, Cell Biology, Metabolism & Cancer - Cellbiology, Research Department OH - Biomolecular Health Sciences, Lozano-Andrés, Estefanía, Enciso-Martinez, Agustin, Gijsbers, Abril, Ridolfi, Andrea, Van Niel, Guillaume, Libregts, Sten F W M, Pinheiro, Cláudio, van Herwijnen, Martijn J C, Hendrix, An, Brucale, Marco, Valle, Francesco, Peters, Peter J, Otto, Cees, Arkesteijn, Ger J A, Wauben, Marca H M, IOV Facs, Celbiologie, Cell Biology, Metabolism & Cancer - Cellbiology, Research Department OH - Biomolecular Health Sciences, Lozano-Andrés, Estefanía, Enciso-Martinez, Agustin, Gijsbers, Abril, Ridolfi, Andrea, Van Niel, Guillaume, Libregts, Sten F W M, Pinheiro, Cláudio, van Herwijnen, Martijn J C, Hendrix, An, Brucale, Marco, Valle, Francesco, Peters, Peter J, Otto, Cees, Arkesteijn, Ger J A, and Wauben, Marca H M

Published
2023

45. A combined western and bead-based multiplex platform to characterize extracellular vesicles

Author

Chirurgie, CS_Locomotion, Celbiologie, Cell Biology, Metabolism & Cancer - Cellbiology, Locomotion - Surgery (CA), van Maanen, Josette, Bach, Frances C, Braun, Theresa S, Giovanazzi, Alberta, van Balkom, Bas W M, Templin, Markus, Wauben, Marca H M, Tryfonidou, Marianna A, Chirurgie, CS_Locomotion, Celbiologie, Cell Biology, Metabolism & Cancer - Cellbiology, Locomotion - Surgery (CA), van Maanen, Josette, Bach, Frances C, Braun, Theresa S, Giovanazzi, Alberta, van Balkom, Bas W M, Templin, Markus, Wauben, Marca H M, and Tryfonidou, Marianna A

Published
2023

46. Acute joint inflammation induces a sharp increase in the number of synovial fluid EVs and modifies their phospholipid profile

Author

CS_Locomotion, Equine Musculoskeletal Biology, Veterinaire biochemie, Celbiologie, IOV Facs, Dep Clinical Sciences, Cell Biology, Metabolism & Cancer - Metabolomics, Cell Biology, Metabolism & Cancer - Cellbiology, Research Department OH - Biomolecular Health Sciences, Locomotion - Equine Sciences, Varela, Laura, van de Lest, Chris H A, Boere, Janneke, Libregts, Sten F W M, Lozano-Andrés, Estefania, van Weeren, P René, Wauben, Marca H M, CS_Locomotion, Equine Musculoskeletal Biology, Veterinaire biochemie, Celbiologie, IOV Facs, Dep Clinical Sciences, Cell Biology, Metabolism & Cancer - Metabolomics, Cell Biology, Metabolism & Cancer - Cellbiology, Research Department OH - Biomolecular Health Sciences, Locomotion - Equine Sciences, Varela, Laura, van de Lest, Chris H A, Boere, Janneke, Libregts, Sten F W M, Lozano-Andrés, Estefania, van Weeren, P René, and Wauben, Marca H M

Published
2023

47. Methods for the identification and characterization of extracellular vesicles in cardiovascular studies - from exosomes to microvesicles

Author

Sub General Pharmaceutics, Celbiologie, dB&C I&I, Cell Biology, Metabolism & Cancer - Cellbiology, Davidson, Sean M, Boulanger, Chantal M, Aikawa, Elena, Badimon, Lina, Barile, Lucio, Binder, Christoph J, Brisson, Alain, Buzas, Edit, Emanueli, Costanza, Jansen, Felix, Katsur, Miroslava, Lacroix, Romaric, Lim, Sai Kiang, Mackman, Nigel, Mayr, Manuel, Menasché, Philippe, Nieuwland, Rienk, Sahoo, Susmita, Takov, Kaloyan, Thum, Thomas, Vader, Pieter, Wauben, Marca H M, Witwer, Kenneth, Sluijter, Joost P G, Sub General Pharmaceutics, Celbiologie, dB&C I&I, Cell Biology, Metabolism & Cancer - Cellbiology, Davidson, Sean M, Boulanger, Chantal M, Aikawa, Elena, Badimon, Lina, Barile, Lucio, Binder, Christoph J, Brisson, Alain, Buzas, Edit, Emanueli, Costanza, Jansen, Felix, Katsur, Miroslava, Lacroix, Romaric, Lim, Sai Kiang, Mackman, Nigel, Mayr, Manuel, Menasché, Philippe, Nieuwland, Rienk, Sahoo, Susmita, Takov, Kaloyan, Thum, Thomas, Vader, Pieter, Wauben, Marca H M, Witwer, Kenneth, and Sluijter, Joost P G

Published
2023

48. Investigations Into the Immunomodulatory Mechanisms of Human Milk Extracellular Vesicles on CD4+ T Cells

Author

Vincelot, Martin, Wauben, Marca (Thesis Advisor), N/A, Vincelot, Martin, Wauben, Marca (Thesis Advisor), and N/A

Abstract

From birth onwards, the adaptive immune system of the mucosal surfaces of human infants undergoes a massive increase in antigen exposure. To avoid its over-activation, human milk plays a major role in the establishment of mucosal immune tolerance. Milk Extracellular Vesicles (EVs) were recently hypothesized to contribute to such immunomodulation as they were shown to increase the stimulation threshold required for activation of CD4+ T helper cells. EVs are nanosized lipid-bilayered vesicles known to mediate intercellular communication. The exact mechanisms by which these EVs modulate T cell activation are unknown. However, the transient and reversible dynamics of this inhibition, and the results of a recent milk EV proteomic analysis suggest that the EV contains a ‘ready-to-act’ protein cargo which interferes with signaling pathways of T cell activation upon delivery. To investigate the potentially immunomodulatory nature of the milk EV protein cargo, an in-silico analysis of the proteome was performed to identify the candidates for further analysis. Additionally, a Jurkat reporter cell line was optimized to efficiently measure EV-mediated immunomodulation of three canonical pathways of T cell activation. This read-out system confirmed that milk EVs cause a two-fold reduction in TCR-derived pathways and a three-fold reduction in CD28-derived pathways. It also revealed that milk EVs from allergic donors are not able to inhibit CD4+ T cell activation as well as milk EVs from non-allergic donors. Overall, a better understanding of milk-EV mediated immunomodulation could greatly enhance medical advice on breastfeeding and prevent the plethora of illnesses associated with over-activation of immunity.

Published
2023

49. Methods for the identification and characterization of extracellular vesicles in cardiovascular studies: from exosomes to microvesicles

Author

CDL Research analisten, Circulatory Health, Experimental Cardiology Laboratory, Onderzoek Cardiovasculair Reg. Med., Regenerative Medicine and Stem Cells, Davidson, Sean M., Boulanger, Chantal M., Aikawa, Elena, Badimon, Lina, Barile, Lucio, Binder, Christoph J., Brisson, Alain, Buzas, Edit, Emanueli, Costanza, Jansen, Felix, Katsur, Miroslava, Lacroix, Romaric, Lim, Sai Kiang, Mackman, Nigel, Mayr, Manuel, Menasché, Philippe, Nieuwland, Rienk, Sahoo, Susmita, Takov, Kaloyan, Thum, Thomas, Vader, Pieter, Wauben, Marca H.M., Witwer, Kenneth, Sluijter, Joost P.G., CDL Research analisten, Circulatory Health, Experimental Cardiology Laboratory, Onderzoek Cardiovasculair Reg. Med., Regenerative Medicine and Stem Cells, Davidson, Sean M., Boulanger, Chantal M., Aikawa, Elena, Badimon, Lina, Barile, Lucio, Binder, Christoph J., Brisson, Alain, Buzas, Edit, Emanueli, Costanza, Jansen, Felix, Katsur, Miroslava, Lacroix, Romaric, Lim, Sai Kiang, Mackman, Nigel, Mayr, Manuel, Menasché, Philippe, Nieuwland, Rienk, Sahoo, Susmita, Takov, Kaloyan, Thum, Thomas, Vader, Pieter, Wauben, Marca H.M., Witwer, Kenneth, and Sluijter, Joost P.G.

Published
2023

50. A Combined Western and Bead-Based Multiplex Platform to Characterize Extracellular Vesicles

Author

MS Nefrologie, Circulatory Health, van Maanen, Josette C., Bach, Frances C., Braun, Theresa S., Giovanazzi, Alberta, van Balkom, Bas W.M., Templin, Markus, Wauben, Marca H.M., Tryfonidou, Marianna A., MS Nefrologie, Circulatory Health, van Maanen, Josette C., Bach, Frances C., Braun, Theresa S., Giovanazzi, Alberta, van Balkom, Bas W.M., Templin, Markus, Wauben, Marca H.M., and Tryfonidou, Marianna A.

Published
2023

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