Nanosized UCMSC-derived extracellular vesicles but not conditioned medium exclusively inhibit the inflammatory response of stimulated T cells: implications for nanomedicine

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...

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Autores: Monguió-Tortajada, Marta|||0000-0003-2125-0810, Rudilla, F.., Gálvez-Montón, Carolina|||0000-0003-2254-9371, Pujal, Josep Maria, Aran, Gemma|||0000-0003-2005-8843, Sanjurjo, Lucía|||0000-0003-4006-8010, Franquesa, Marcella|||0000-0002-1287-8908, Sarrias, Maria-Rosa|||0000-0001-6929-8069, Bayés-Genís, Antoni|||0000-0002-3044-197X, Borràs i Serres, Francesc Enric|||0000-0003-4038-1912
Tipo de recurso: artículo
Fecha de publicación:2017
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:196273
Acceso en línea:https://ddd.uab.cat/record/196273
https://dx.doi.org/urn:doi:10.7150/thno.16154
Access Level:acceso abierto
Palabra clave:Nanosized extracellular vesicles
Exosomes
Inflammation
Umbilical cord mesenchymal stem cell
Immunomodulation
Size exclusion chromatography
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oai_identifier_str oai:ddd.uab.cat:196273
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Nanosized UCMSC-derived extracellular vesicles but not conditioned medium exclusively inhibit the inflammatory response of stimulated T cells: implications for nanomedicine
title Nanosized UCMSC-derived extracellular vesicles but not conditioned medium exclusively inhibit the inflammatory response of stimulated T cells: implications for nanomedicine
spellingShingle Nanosized UCMSC-derived extracellular vesicles but not conditioned medium exclusively inhibit the inflammatory response of stimulated T cells: implications for nanomedicine
Monguió-Tortajada, Marta|||0000-0003-2125-0810
Nanosized extracellular vesicles
Exosomes
Inflammation
Umbilical cord mesenchymal stem cell
Immunomodulation
Size exclusion chromatography
title_short Nanosized UCMSC-derived extracellular vesicles but not conditioned medium exclusively inhibit the inflammatory response of stimulated T cells: implications for nanomedicine
title_full Nanosized UCMSC-derived extracellular vesicles but not conditioned medium exclusively inhibit the inflammatory response of stimulated T cells: implications for nanomedicine
title_fullStr Nanosized UCMSC-derived extracellular vesicles but not conditioned medium exclusively inhibit the inflammatory response of stimulated T cells: implications for nanomedicine
title_full_unstemmed Nanosized UCMSC-derived extracellular vesicles but not conditioned medium exclusively inhibit the inflammatory response of stimulated T cells: implications for nanomedicine
title_sort Nanosized UCMSC-derived extracellular vesicles but not conditioned medium exclusively inhibit the inflammatory response of stimulated T cells: implications for nanomedicine
dc.creator.none.fl_str_mv Monguió-Tortajada, Marta|||0000-0003-2125-0810
Rudilla, F..
Gálvez-Montón, Carolina|||0000-0003-2254-9371
Pujal, Josep Maria
Aran, Gemma|||0000-0003-2005-8843
Sanjurjo, Lucía|||0000-0003-4006-8010
Franquesa, Marcella|||0000-0002-1287-8908
Sarrias, Maria-Rosa|||0000-0001-6929-8069
Bayés-Genís, Antoni|||0000-0002-3044-197X
Borràs i Serres, Francesc Enric|||0000-0003-4038-1912
author Monguió-Tortajada, Marta|||0000-0003-2125-0810
author_facet Monguió-Tortajada, Marta|||0000-0003-2125-0810
Rudilla, F..
Gálvez-Montón, Carolina|||0000-0003-2254-9371
Pujal, Josep Maria
Aran, Gemma|||0000-0003-2005-8843
Sanjurjo, Lucía|||0000-0003-4006-8010
Franquesa, Marcella|||0000-0002-1287-8908
Sarrias, Maria-Rosa|||0000-0001-6929-8069
Bayés-Genís, Antoni|||0000-0002-3044-197X
Borràs i Serres, Francesc Enric|||0000-0003-4038-1912
author_role author
author2 Rudilla, F..
Gálvez-Montón, Carolina|||0000-0003-2254-9371
Pujal, Josep Maria
Aran, Gemma|||0000-0003-2005-8843
Sanjurjo, Lucía|||0000-0003-4006-8010
Franquesa, Marcella|||0000-0002-1287-8908
Sarrias, Maria-Rosa|||0000-0001-6929-8069
Bayés-Genís, Antoni|||0000-0002-3044-197X
Borràs i Serres, Francesc Enric|||0000-0003-4038-1912
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Nanosized extracellular vesicles
Exosomes
Inflammation
Umbilical cord mesenchymal stem cell
Immunomodulation
Size exclusion chromatography
topic Nanosized extracellular vesicles
Exosomes
Inflammation
Umbilical cord mesenchymal stem cell
Immunomodulation
Size exclusion chromatography
description 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.
publishDate 2017
dc.date.none.fl_str_mv 2
2017-01-01
2017
2017-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/196273
https://dx.doi.org/urn:doi:10.7150/thno.16154
url https://ddd.uab.cat/record/196273
https://dx.doi.org/urn:doi:10.7150/thno.16154
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 FISPI13/00050
Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 FISPI14/01682
Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2014/SGR-804
Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2014/SGR-699
Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 REDinREN/16/0009
Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 SAF2014-59892-R
Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 RD12/0019/0029
Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2014FIB00649
Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2014BPB00118
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by-nc/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by-nc/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
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repository.mail.fl_str_mv
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spelling Nanosized UCMSC-derived extracellular vesicles but not conditioned medium exclusively inhibit the inflammatory response of stimulated T cells: implications for nanomedicineMonguió-Tortajada, Marta|||0000-0003-2125-0810Rudilla, F..Gálvez-Montón, Carolina|||0000-0003-2254-9371Pujal, Josep MariaAran, Gemma|||0000-0003-2005-8843Sanjurjo, Lucía|||0000-0003-4006-8010Franquesa, Marcella|||0000-0002-1287-8908Sarrias, Maria-Rosa|||0000-0001-6929-8069Bayés-Genís, Antoni|||0000-0002-3044-197XBorràs i Serres, Francesc Enric|||0000-0003-4038-1912Nanosized extracellular vesiclesExosomesInflammationUmbilical cord mesenchymal stem cellImmunomodulationSize exclusion chromatographyUndesired 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. 22017-01-0120172017-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/196273https://dx.doi.org/urn:doi:10.7150/thno.16154reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengInstituto de Salud Carlos III https://doi.org/10.13039/501100004587 FISPI13/00050Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 FISPI14/01682Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2014/SGR-804Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2014/SGR-699Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 REDinREN/16/0009Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 SAF2014-59892-RMinisterio de Economía y Competitividad https://doi.org/10.13039/501100003329 RD12/0019/0029Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2014FIB00649Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2014BPB00118open accesshttp://purl.org/coar/access_right/c_abf2Aquest 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.https://creativecommons.org/licenses/by-nc/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:1962732026-06-06T12:50:31Z
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