N-Glycans in Immortalized Mesenchymal Stromal Cell-Derived Extracellular Vesicles Are Critical for EV-Cell Interaction and Functional Activation of Endothelial Cells.

Autor: Clos-Sansalvador M; REMAR-IGTP Group, Germans Trias i Pujol Research Institute (IGTP) & Nephrology Department, University Hospital Germans Trias i Pujol (HUGTiP), Can Ruti Campus, 08916 Badalona, Spain.; Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona (UAB), 08193 Bellaterra, Spain., Garcia SG; REMAR-IGTP Group, Germans Trias i Pujol Research Institute (IGTP) & Nephrology Department, University Hospital Germans Trias i Pujol (HUGTiP), Can Ruti Campus, 08916 Badalona, Spain.; Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona (UAB), 08193 Bellaterra, Spain., Morón-Font M; REMAR-IGTP Group, Germans Trias i Pujol Research Institute (IGTP) & Nephrology Department, University Hospital Germans Trias i Pujol (HUGTiP), Can Ruti Campus, 08916 Badalona, Spain., Williams C; CIC biomaGUNE, Glycotechnology Group, Basque Research and Technology Alliance (BRTA), 20014 San Sebastian, Spain.; Exosomes Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), 20850 Derio, Spain., Reichardt NC; CIC biomaGUNE, Glycotechnology Group, Basque Research and Technology Alliance (BRTA), 20014 San Sebastian, Spain.; Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), 20014 San Sebastian, Spain., Falcón-Pérez JM; Exosomes Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), 20850 Derio, Spain.; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 41092 Madrid, Spain.; Basque Foundation for Science (IKERBASQUE), 48009 Bilbao, Spain., Bayes-Genis A; ICREC Research Program, Health Science Research Institute Germans Trias i Pujol, Can Ruti Campus, 08916 Badalona, Spain.; iCor, Cardiology Service, Germans Trias i Pujol University Hospital, 08916 Badalona, Spain.; CIBERCV, Instituto de Salud Carlos III, 41092 Madrid, Spain.; Department of Medicine, Universitat Autònoma de Barcelona (UAB), 08193 Barcelona, Spain., Roura S; ICREC Research Program, Health Science Research Institute Germans Trias i Pujol, Can Ruti Campus, 08916 Badalona, Spain.; CIBERCV, Instituto de Salud Carlos III, 41092 Madrid, Spain.; Faculty of Medicine, University of Vic-Central University of Catalonia (UVic-UCC), 08500 Vic, Spain., Franquesa M; REMAR-IGTP Group, Germans Trias i Pujol Research Institute (IGTP) & Nephrology Department, University Hospital Germans Trias i Pujol (HUGTiP), Can Ruti Campus, 08916 Badalona, Spain., Monguió-Tortajada M; REMAR-IGTP Group, Germans Trias i Pujol Research Institute (IGTP) & Nephrology Department, University Hospital Germans Trias i Pujol (HUGTiP), Can Ruti Campus, 08916 Badalona, Spain.; ICREC Research Program, Health Science Research Institute Germans Trias i Pujol, Can Ruti Campus, 08916 Badalona, Spain.; iCor, Cardiology Service, Germans Trias i Pujol University Hospital, 08916 Badalona, Spain., Borràs FE; REMAR-IGTP Group, Germans Trias i Pujol Research Institute (IGTP) & Nephrology Department, University Hospital Germans Trias i Pujol (HUGTiP), Can Ruti Campus, 08916 Badalona, Spain.; Department of Cell Biology, Physiology and Immunology, Universitat de Barcelona (UB), 08007 Barcelona, Spain.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2022 Aug 23; Vol. 23 (17). Date of Electronic Publication: 2022 Aug 23.
DOI: 10.3390/ijms23179539
Abstrakt: Mesenchymal stromal cell-derived extracellular vesicles (MSC-EV) are widely considered as a cell-free therapeutic alternative to MSC cell administration, due to their immunomodulatory and regenerative properties. However, the interaction mechanisms between EV and target cells are not fully understood. The surface glycans could be key players in EV-cell communication, being specific molecular recognition patterns that are still little explored. In this study, we focused on the role of N-glycosylation of MSC-EV as mediators of MSC-EV and endothelial cells' interaction for subsequent EV uptake and the induction of cell migration and angiogenesis. For that, EV from immortalized Wharton's Jelly MSC (iWJ-MSC-EV) were isolated by size exclusion chromatography (SEC) and treated with the glycosidase PNGase-F in order to remove wild-type N-glycans. Then, CFSE-labelled iWJ-MSC-EV were tested in the context of in vitro capture, agarose-spot migration and matrigel-based tube formation assays, using HUVEC. As a result, we found that the N-glycosylation in iWJ-MSC-EV is critical for interaction with HUVEC cells. iWJ-MSC-EV were captured by HUVEC, stimulating their tube-like formation ability and promoting their recruitment. Conversely, the removal of N-glycans through PNGase-F treatment reduced all of these functional activities induced by native iWJ-MSC-EV. Finally, comparative lectin arrays of iWJ-MSC-EV and PNGase-F-treated iWJ-MSC-EV found marked differences in the surface glycosylation pattern, particularly in N-acetylglucosamine, mannose, and fucose-binding lectins. Taken together, our results highlight the importance of N-glycans in MSC-EV to permit EV-cell interactions and associated functions.
Databáze: MEDLINE
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