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Mesenchymal stem cells-derived exosomes are more immunosuppressive than microparticles in inflammatory arthritis

Objectives: Mesenchymal stem cells (MSCs) release extracellular vesicles (EVs) that display a therapeutic effect in inflammatory disease models. Although MSCs can prevent arthritis, the role of MSCs-derived EVs has never been reported in rheumatoid arthritis. This prompted us to compare the function...

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Autores principales: Cosenza, Stella, Toupet, Karine, Maumus, Marie, Luz-Crawford, Patricia, Blanc-Brude, Olivier, Jorgensen, Christian, Noël, Danièle
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5835945/
https://www.ncbi.nlm.nih.gov/pubmed/29507629
http://dx.doi.org/10.7150/thno.21072
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author Cosenza, Stella
Toupet, Karine
Maumus, Marie
Luz-Crawford, Patricia
Blanc-Brude, Olivier
Jorgensen, Christian
Noël, Danièle
author_facet Cosenza, Stella
Toupet, Karine
Maumus, Marie
Luz-Crawford, Patricia
Blanc-Brude, Olivier
Jorgensen, Christian
Noël, Danièle
author_sort Cosenza, Stella
collection PubMed
description Objectives: Mesenchymal stem cells (MSCs) release extracellular vesicles (EVs) that display a therapeutic effect in inflammatory disease models. Although MSCs can prevent arthritis, the role of MSCs-derived EVs has never been reported in rheumatoid arthritis. This prompted us to compare the function of exosomes (Exos) and microparticles (MPs) isolated from MSCs and investigate their immunomodulatory function in arthritis. Methods: MSCs-derived Exos and MPs were isolated by differential ultracentrifugation. Immunosuppressive effects of MPs or Exos were investigated on T and B lymphocytes in vitro and in the Delayed-Type Hypersensitivity (DTH) and Collagen-Induced Arthritis (CIA) models. Results: Exos and MPs from MSCs inhibited T lymphocyte proliferation in a dose-dependent manner and decreased the percentage of CD4(+) and CD8(+) T cell subsets. Interestingly, Exos increased Treg cell populations while parental MSCs did not. Conversely, plasmablast differentiation was reduced to a similar extent by MSCs, Exos or MPs. IFN-γ priming of MSCs before vesicles isolation did not influence the immunomodulatory function of isolated Exos or MPs. In DTH, we observed a dose-dependent anti-inflammatory effect of MPs and Exos, while in the CIA model, Exos efficiently decreased clinical signs of inflammation. The beneficial effect of Exos was associated with fewer plasmablasts and more Breg-like cells in lymph nodes. Conclusions: Both MSCs-derived MPs and Exos exerted an anti-inflammatory role on T and B lymphocytes independently of MSCs priming. However, Exos were more efficient in suppressing inflammation in vivo. Our work is the first demonstration of the therapeutic potential of MSCs-derived EVs in inflammatory arthritis.
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spelling pubmed-58359452018-03-05 Mesenchymal stem cells-derived exosomes are more immunosuppressive than microparticles in inflammatory arthritis Cosenza, Stella Toupet, Karine Maumus, Marie Luz-Crawford, Patricia Blanc-Brude, Olivier Jorgensen, Christian Noël, Danièle Theranostics Research Paper Objectives: Mesenchymal stem cells (MSCs) release extracellular vesicles (EVs) that display a therapeutic effect in inflammatory disease models. Although MSCs can prevent arthritis, the role of MSCs-derived EVs has never been reported in rheumatoid arthritis. This prompted us to compare the function of exosomes (Exos) and microparticles (MPs) isolated from MSCs and investigate their immunomodulatory function in arthritis. Methods: MSCs-derived Exos and MPs were isolated by differential ultracentrifugation. Immunosuppressive effects of MPs or Exos were investigated on T and B lymphocytes in vitro and in the Delayed-Type Hypersensitivity (DTH) and Collagen-Induced Arthritis (CIA) models. Results: Exos and MPs from MSCs inhibited T lymphocyte proliferation in a dose-dependent manner and decreased the percentage of CD4(+) and CD8(+) T cell subsets. Interestingly, Exos increased Treg cell populations while parental MSCs did not. Conversely, plasmablast differentiation was reduced to a similar extent by MSCs, Exos or MPs. IFN-γ priming of MSCs before vesicles isolation did not influence the immunomodulatory function of isolated Exos or MPs. In DTH, we observed a dose-dependent anti-inflammatory effect of MPs and Exos, while in the CIA model, Exos efficiently decreased clinical signs of inflammation. The beneficial effect of Exos was associated with fewer plasmablasts and more Breg-like cells in lymph nodes. Conclusions: Both MSCs-derived MPs and Exos exerted an anti-inflammatory role on T and B lymphocytes independently of MSCs priming. However, Exos were more efficient in suppressing inflammation in vivo. Our work is the first demonstration of the therapeutic potential of MSCs-derived EVs in inflammatory arthritis. Ivyspring International Publisher 2018-02-03 /pmc/articles/PMC5835945/ /pubmed/29507629 http://dx.doi.org/10.7150/thno.21072 Text en © Ivyspring International Publisher This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Cosenza, Stella
Toupet, Karine
Maumus, Marie
Luz-Crawford, Patricia
Blanc-Brude, Olivier
Jorgensen, Christian
Noël, Danièle
Mesenchymal stem cells-derived exosomes are more immunosuppressive than microparticles in inflammatory arthritis
title Mesenchymal stem cells-derived exosomes are more immunosuppressive than microparticles in inflammatory arthritis
title_full Mesenchymal stem cells-derived exosomes are more immunosuppressive than microparticles in inflammatory arthritis
title_fullStr Mesenchymal stem cells-derived exosomes are more immunosuppressive than microparticles in inflammatory arthritis
title_full_unstemmed Mesenchymal stem cells-derived exosomes are more immunosuppressive than microparticles in inflammatory arthritis
title_short Mesenchymal stem cells-derived exosomes are more immunosuppressive than microparticles in inflammatory arthritis
title_sort mesenchymal stem cells-derived exosomes are more immunosuppressive than microparticles in inflammatory arthritis
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5835945/
https://www.ncbi.nlm.nih.gov/pubmed/29507629
http://dx.doi.org/10.7150/thno.21072
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