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. Hospital Universitari Germans Trias i Pujol)
Rudilla, F.. (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, Gemma (Institut Germans Trias i Pujol)
Sanjurjo, Lucía (Institut Germans Trias i Pujol)
Franquesa, Marcella (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Sarrias, Maria-Rosa (Institut Germans Trias i Pujol)
Bayés-Genís, Antoni (Universitat Autònoma de Barcelona. Departament de Medicina)
Borràs i Serres, Francesc Enric (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)

Fecha:	2017
Resumen:	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.
Ayudas:	Instituto de Salud Carlos III FISPI13/00050 Instituto de Salud Carlos III FISPI14/01682 Agència de Gestió d'Ajuts Universitaris i de Recerca 2014/SGR-804 Agència de Gestió d'Ajuts Universitaris i de Recerca 2014/SGR-699 Instituto de Salud Carlos III REDinREN/16/0009 Ministerio de Economía y Competitividad SAF2014-59892-R Ministerio de Economía y Competitividad RD12/0019/0029 Agència de Gestió d'Ajuts Universitaris i de Recerca 2014FIB00649 Agència de Gestió d'Ajuts Universitaris i de Recerca 2014BPB00118
Nota:	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).
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, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Nanosized extracellular vesicles ; Exosomes ; Inflammation ; Umbilical cord mesenchymal stem cell ; Immunomodulation ; Size exclusion chromatography
Publicado en:	Theranostics, Vol. 7 Núm. 2 (2017) , p. 270-284, ISSN 1838-7640

DOI: 10.7150/thno.16154
PMID: 28042333

15 p, 2.3 MB

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Documentos de investigación > Documentos de los grupos de investigación de la UAB > Centros y grupos de investigación (producción científica) > Ciencias de la salud y biociencias > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
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