Surface protein profiling of milk and serum extracellular vesicles unveils body fluid-specific signatures
Giovanazzi, Alberta; van Herwijnen, Martijn J C; Kleinjan, Marije; van der Meulen, Gerbrich N; Wauben, Marca H M
(2023) Scientific Reports, volume 13, issue 1, pp. 1 - 13
(Article)
Abstract
Cell-derived extracellular vesicles (EVs) are currently in the limelight as potential disease biomarkers. The promise of EV-based liquid biopsy resides in the identification of specific disease-associated EV signatures. Knowing the reference EV profile of a body fluid can facilitate the identification of such disease-associated EV-biomarkers. With this aim, we purified
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EVs from paired human milk and serum samples and used the MACSPlex bead-based flow-cytometry assay to capture EVs on bead-bound antibodies specific for a certain surface protein, followed by EV detection by the tetraspanins CD9, CD63, and CD81. Using this approach we identified body fluid-specific EV signatures, e.g. breast epithelial cell signatures in milk EVs and platelet signatures in serum EVs, as well as body fluid-specific markers associated to immune cells and stem cells. Interestingly, comparison of pan-tetraspanin detection (simultaneous CD9, CD63 and CD81 detection) and single tetraspanin detection (detection by CD9, CD63 or CD81) also unveiled body fluid-specific tetraspanin distributions on EVs. Moreover, certain EV surface proteins were associated with a specific tetraspanin distribution, which could be indicative of the biogenesis route of this EV subset. Altogether, the identified body fluid-specific EV profiles can contribute to study EV profile deviations in these fluids during disease processes.
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Keywords: Breast-milk, Cell, Exosomes, Markers, Populations, General
ISSN: 2045-2322
Publisher: NLM (Medline)
Note: Funding Information: We thank Ger Arkesteijn for his constant support and the use of the Flow Cytometry Facility (Faculty of Veterinary Medicine, Utrecht University, The Netherlands) and Johan Garssen (Department of Pharmaceutical Sciences, Faculty of Science, Utrecht University, The Netherlands and Nutricia Research Centre for Specialized Nutrition, The Netherlands), Frank A. Redegeld (Department of Pharmaceutical Sciences, Faculty of Science, Utrecht University, The Netherlands), Ruurd H. van Elburg (Department of Pediatrics, Emma Children's Hospital/Academic Medical Center, Amsterdam, The Netherlands), and Arianne van Bruggen-de Haan (Paediatric Allergy Centre, Department of Paediatrics, Martini Hospital, Groningen, The Netherlands) for their contributions to the clinical ACCESS study from which biobanked samples were used in this study. Funding Information: The research of A.G. was supported by the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie Grant agreement No 722148. The research of M.J.C.H. and the clinical ACCESS study (Comparison of Human Milk Extracellular Vesicles in Allergic and Non-allergic Mothers (ACCESS)) was funded by a partnership grant of the Dutch Technology foundation STW between Nutricia Research and Utrecht University (STW project 11676: Exosome-based biomarker profiling of breast milk: Definition of predictive immunomodulating biomarker profiles for the management of allergic disease development in infants). Publisher Copyright: © 2023, The Author(s).
(Peer reviewed)
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