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Página principal > Artículos > Artículos publicados > Immunomodulatory effect of MSC on B cells is independent of secreted extracellular vesicles |
Fecha: | 2019 |
Resumen: | Mesenchymal stem or stromal cells (MSC) have proven immunomodulatory properties toward B cell activation and induce regulatory B cells (Breg), through a dual mechanism of action that relies both on cell contact and secreted factors. One of them are MSC-derived extracellular vesicles (EVs), membrane nanovesicles that mediate cell communication and typically reflect the phenotype of the cell of origin. MSC-EVs could resemble MSC functions, and are being contemplated as an improved alternative to the MSC-based immunomodulatory therapy. In the present work, we focused on the factors secreted by MSC and aimed to elucidate the putative role of MSC-EVs in the immunomodulation of B cells. EVs and soluble protein-enriched fractions (PF) were isolated from MSC-conditioned medium (CM) using size-exclusion chromatography (SEC) and their capacity to modulate B cell activation, induction of Breg and B cell proliferation was compared to that of the whole MSCs. Co-culture with MSC or unfractionated CM induced naïve and CD24hiCD38hi, IL-10 producing (Breg) phenotypes on B cells while not affecting proliferation. MSC-PF had a comparable effect to MSCs, inducing a naïve phenotype, and even though they did not induce the shift toward a CD24hiCD38hi population, MSC-PF fostered IL-10 production by B cells. Conversely, MSC-EVs failed to promote naïve B cells and to reduce memory B cells. MSC-EVs induced CD24hiCD38hi B cells to a similar extent of that of MSC, but not bona fide Bregs since they did not produce IL-10. Our results show that B cell modulation by MSC is partially mediated by soluble factors other than EVs. |
Ayudas: | Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-301 Instituto de Salud Carlos III RD16/0009 Instituto de Salud Carlos III PI17/00335 Ministerio de Ciencia e Innovación FPU17/01444 |
Nota: | Altres ajuts: this work was supported in part by Fundació La Marató de TV3 (201516-10, 201502-30). MM-T is sponsored by the PERIS (SLT002/16/00234) from the Generalitat de Catalunya; FB is a researcher from Fundació Institut de Recerca en Ciències de la Salut Germans Trias i Pujol, supported by the Health Department of the Catalan Government (Direcció General de Recerca i Innovació, Department Salut, Generalitat de Catalunya) and MF is funded by the Catalan Health Department (Generalitat de Catalunya) contract PERIS (SLT002/16/00069). |
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 stromal cells ; Exosome ; Regulatory B cell ; Immunosuppression ; Memory B cell ; Ev isolation |
Publicado en: | Frontiers in immunology, Vol. 10 (June 2019) , art. 1288, ISSN 1664-3224 |
Obra relacionada: | Carreras-Planella, Laura; Monguió-Tortajada, Marta; Borràs i Serres, Francesc Enric; Franquesa, Marcella; «Corrigendum: Immunomodulatory Effect of MSC on B Cells Is Independent of Secreted Extracellular Vesicles». Frontiers in immunology, Vol. 10 (october 2019) https://doi.org/10.3389/fimmu.2019.02413 |
8 p, 1.4 MB |