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Nanosized UCMSC-derived extracellular vesicles but not conditioned medium exclusively inhibit the inflammatory response of stimulated T cells: implications for nanomedicine
Monguió Tortajada, Marta (Institut Germans Trias i Pujol)
Roura, Santiago (Institut Germans Trias i Pujol)
Gálvez Montón, Carolina (Institut Germans Trias i Pujol)
Pujal, Josep Maria (Universitat de Girona. Laboratori de processament cel·lular)
Aran Canals, Gemma (Institut Germans Trias i Pujol)
Sanjurjo, Lucía (Institut Germans Trias i Pujol)
Franquesa, Marcel·la (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Sarrias, Maria-Rosa (Institut Germans Trias i Pujol)
Bayes Genis, Antoni (Universitat Autònoma de Barcelona. Departament de Medicina)
Borràs, Francesc E. (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)

Date: 2017
Abstract: Undesired immune responses have drastically hampered outcomes after allogeneic organ transplantation and cell therapy, and also lead to inflammatory diseases and autoimmunity. Umbilical cord mesenchymal stem cells (UCMSCs) have powerful regenerative and immunomodulatory potential, and their secreted extracellular vesicles (EVs) are envisaged as a promising natural source of nanoparticles to increase outcomes in organ transplantation and control inflammatory diseases. However, poor EV preparations containing highly-abundant soluble proteins may mask genuine vesicular-associated functions and provide misleading data. Here, we used Size-Exclusion Chromatography (SEC) to successfully isolate EVs from UCMSCs-conditioned medium. These vesicles were defined as positive for CD9, CD63, CD73 and CD90, and their size and morphology characterized by NTA and cryo-EM. Their immunomodulatory potential was determined in polyclonal T cell proliferation assays, analysis of cytokine profiles and in the skewing of monocyte polarization. In sharp contrast to the non-EV containing fractions, to the complete conditioned medium and to ultracentrifuged pellet, SEC-purified EVs from UCMSCs inhibited T cell proliferation, resembling the effect of parental UCMSCs. Moreover, while SEC-EVs did not induce cytokine response, the non-EV fractions, conditioned medium and ultracentrifuged pellet promoted the secretion of pro-inflammatory cytokines by polyclonally stimulated T cells and supported Th17 polarization. In contrast, EVs did not induce monocyte polarization, but the non-EV fraction induced CD163 and CD206 expression and TNF-α production in monocytes. These findings increase the growing evidence confirming that EVs are an active component of MSC's paracrine immunosuppressive function and affirm their potential for therapeutics in nanomedicine. In addition, our results highlight the importance of well-purified and defined preparations of MSC-derived EVs to achieve the immunosuppressive effect.
Note: Altres ajuts: La Marató TV3 (201502 i 201516). This work has been developed in the context of AdvanceCat with the support of ACCIÓ (Catalonia Trade & Investment; Generalitat de Catalunya) under the Catalonian ERDF operational program (European Regional Development Fund) 2014-2020. FEB is sponsored by the "Researchers Stabilization Program" from the Spanish "Sistema Nacional de Salud" (SNS-ISCIII) and "Direcció d'Estratègia i Coordinació" Catalan Health Department (CES07/015).
Note: Número d'acord de subvenció ISCIII/FIS PI13/00050
Note: Número d'acord de subvenció ISCIII/FIS PI14/01682
Note: Número d'acord de subvenció AGAUR/SGR/2014SGR804
Note: Número d'acord de subvenció AGAUR/SGR/2014SGR699
Note: Número d'acord de subvenció ISCIII/REDinREN/16/0009
Note: Número d'acord de subvenció MINECO/SAF2014-59892-R
Note: Número d'acord de subvenció MINECO/RD12/0019/0029
Note: Número d'acord de subvenció AGAUR/2014FI B00649
Note: Número d'acord de subvenció AGAUR/2014BP B00118
Rights: 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, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. Creative Commons
Language: Anglès
Document: article ; recerca ; publishedVersion
Subject: Nanosized extracellular vesicles ; Exosomes ; Inflammation ; Umbilical cord mesenchymal stem cell ; Immunomodulation ; Size exclusion chromatography
Published in: , Vol. 7 Núm. 2 (2017) , p. 270-284, ISSN 1838-7640

DOI: 10.7150/thno.16154
PMID: 28042333

15 p, 2.3 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (scientific output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
Articles > Research articles
Articles > Published articles

 Record created 2018-10-04, last modified 2020-08-30

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