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| Página principal > Artículos > Artículos publicados > N-Glycans in Immortalized Mesenchymal Stromal Cell-Derived Extracellular Vesicles Are Critical for EV-Cell Interaction and Functional Activation of Endothelial Cells |
(Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia) (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia) (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol) (Basque Foundation for Science) (Universitat Autònoma de Barcelona. Departament de Medicina) (Universitat de Vic - Universitat Central de Catalunya) (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol) (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol) (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
| Fecha: | 2022 |
| Resumen: | 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. |
| Ayudas: | Agencia Estatal de Investigación PID2019-110137RB-I00 Instituto de Salud Carlos III ICI20/00135 Agencia Estatal de Investigación RED2018-102411-T Instituto de Salud Carlos III RD21/0017/0022 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-483 Agencia Estatal de Investigación PID2020-117552RB-I00 Agencia Estatal de Investigación RTC-2017-6126-1 Agencia Estatal de Investigación MDM-2017-0720 Instituto de Salud Carlos III FI20/00021 Instituto de Salud Carlos III MS19/00018 |
| Derechos: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.  |
| Lengua: | Anglès |
| Documento: | Article ; recerca ; Versió publicada |
| Materia: | Mesenchymal stem/stromal cells ; Extracellular vesicles ; Exosomes ; Glycans ; Glycosylation ; Lectins |
| Publicado en: | International journal of molecular sciences, Vol. 23, Issue 17 (August 2022) , art. 9539, ISSN 1422-0067 |
