Improving the therapeutic profile of MSCs: Cytokine priming reduces donor-dependent heterogeneity and enhances their immunomodulatory capacity

Introduction: MSCs exhibit regenerative, anti-inflammatory and immunomodulatory properties due to the large amount of cytokines, chemokines and growth factors they secrete. MSCs have been extensively evaluated in clinical trials, however, in some cases their therapeutic effects are variable. Therefo...

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Autores: Valencia Mahón, Jaris, Yáñez, Rosa, Muntión, Sandra, Fernández García, María, Martín Rufino, Jorge Diego, Zapata González, Agustín Gregorio, Bueren, Juan A., Vicente López, María Ángeles, Sánchez Guijo, Fermin
Tipo de recurso: artículo
Fecha de publicación:2025
País:España
Institución:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/133330
Acceso en línea:https://hdl.handle.net/20.500.14352/133330
Access Level:acceso abierto
Palabra clave:612.017
Ciencias Biomédicas
Biología celular (Biología)
Medicina
2412 Inmunología
2407 Biología Celular
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spelling Improving the therapeutic profile of MSCs: Cytokine priming reduces donor-dependent heterogeneity and enhances their immunomodulatory capacityValencia Mahón, JarisYáñez, RosaMuntión, SandraFernández García, MaríaMartín Rufino, Jorge DiegoZapata González, Agustín GregorioBueren, Juan A.Vicente López, María ÁngelesSánchez Guijo, Fermin612.017Ciencias BiomédicasBiología celular (Biología)Medicina2412 Inmunología2407 Biología CelularIntroduction: MSCs exhibit regenerative, anti-inflammatory and immunomodulatory properties due to the large amount of cytokines, chemokines and growth factors they secrete. MSCs have been extensively evaluated in clinical trials, however, in some cases their therapeutic effects are variable. Therefore, strategies to improve their therapeutic potential, such as preconditioning with proinflammatory factors, have been proposed. Several priming approaches have provided non-conclusive results, and the duration of priming effects on MSC properties or their response to a second inflammatory stimulus have not been fully addressed.Methods: We have investigated the impact of triple cytokine priming in MSCs on their characterization and viability, their transcriptomic profile, the functionality of innate and acquired immune cells, as well as the maintenance of the response to priming over time, their subsequent responsiveness to a second inflammatory stimulus.Results: Priming MSCs with proinflammatory cytokines (CK-MSCs) do not modify the differentiation capacity of MSCs, nor their immunophenotype and viability. Moreover, cytokine priming enhances the anti-inflammatory and immunomodulatory properties of MSCs against NK and dendritic cells, while maintaining the same T cell immunomodulatory capacity as unstimulated MSCs. Thus, they decrease T-lymphocytes and NK cell proliferation, inhibit the differentiation and allostimulatory capacity of dendritic cells and promote the differentiation of monocytes with an immunosuppressive profile. In addition, we have shown for the first time that proinflammatory priming reduces the variability between different donors and MSC origins. Finally, the effect on CK-MSC is maintained over time and even after a secondary inflammatory stimulus.Conclusions: Cytokine-priming improves the therapeutic potential of MSCs and reduces inter-donor variability.Frontiers MediaUniversidad Complutense de Madrid20252025-02-1720252025-02-17journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.14352/133330reponame:Docta Complutenseinstname:Universidad Complutense de Madrid (UCM)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:docta.ucm.es:20.500.14352/1333302026-06-02T12:44:21Z
dc.title.none.fl_str_mv Improving the therapeutic profile of MSCs: Cytokine priming reduces donor-dependent heterogeneity and enhances their immunomodulatory capacity
title Improving the therapeutic profile of MSCs: Cytokine priming reduces donor-dependent heterogeneity and enhances their immunomodulatory capacity
spellingShingle Improving the therapeutic profile of MSCs: Cytokine priming reduces donor-dependent heterogeneity and enhances their immunomodulatory capacity
Valencia Mahón, Jaris
612.017
Ciencias Biomédicas
Biología celular (Biología)
Medicina
2412 Inmunología
2407 Biología Celular
title_short Improving the therapeutic profile of MSCs: Cytokine priming reduces donor-dependent heterogeneity and enhances their immunomodulatory capacity
title_full Improving the therapeutic profile of MSCs: Cytokine priming reduces donor-dependent heterogeneity and enhances their immunomodulatory capacity
title_fullStr Improving the therapeutic profile of MSCs: Cytokine priming reduces donor-dependent heterogeneity and enhances their immunomodulatory capacity
title_full_unstemmed Improving the therapeutic profile of MSCs: Cytokine priming reduces donor-dependent heterogeneity and enhances their immunomodulatory capacity
title_sort Improving the therapeutic profile of MSCs: Cytokine priming reduces donor-dependent heterogeneity and enhances their immunomodulatory capacity
dc.creator.none.fl_str_mv Valencia Mahón, Jaris
Yáñez, Rosa
Muntión, Sandra
Fernández García, María
Martín Rufino, Jorge Diego
Zapata González, Agustín Gregorio
Bueren, Juan A.
Vicente López, María Ángeles
Sánchez Guijo, Fermin
author Valencia Mahón, Jaris
author_facet Valencia Mahón, Jaris
Yáñez, Rosa
Muntión, Sandra
Fernández García, María
Martín Rufino, Jorge Diego
Zapata González, Agustín Gregorio
Bueren, Juan A.
Vicente López, María Ángeles
Sánchez Guijo, Fermin
author_role author
author2 Yáñez, Rosa
Muntión, Sandra
Fernández García, María
Martín Rufino, Jorge Diego
Zapata González, Agustín Gregorio
Bueren, Juan A.
Vicente López, María Ángeles
Sánchez Guijo, Fermin
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidad Complutense de Madrid
dc.subject.none.fl_str_mv 612.017
Ciencias Biomédicas
Biología celular (Biología)
Medicina
2412 Inmunología
2407 Biología Celular
topic 612.017
Ciencias Biomédicas
Biología celular (Biología)
Medicina
2412 Inmunología
2407 Biología Celular
description Introduction: MSCs exhibit regenerative, anti-inflammatory and immunomodulatory properties due to the large amount of cytokines, chemokines and growth factors they secrete. MSCs have been extensively evaluated in clinical trials, however, in some cases their therapeutic effects are variable. Therefore, strategies to improve their therapeutic potential, such as preconditioning with proinflammatory factors, have been proposed. Several priming approaches have provided non-conclusive results, and the duration of priming effects on MSC properties or their response to a second inflammatory stimulus have not been fully addressed.Methods: We have investigated the impact of triple cytokine priming in MSCs on their characterization and viability, their transcriptomic profile, the functionality of innate and acquired immune cells, as well as the maintenance of the response to priming over time, their subsequent responsiveness to a second inflammatory stimulus.Results: Priming MSCs with proinflammatory cytokines (CK-MSCs) do not modify the differentiation capacity of MSCs, nor their immunophenotype and viability. Moreover, cytokine priming enhances the anti-inflammatory and immunomodulatory properties of MSCs against NK and dendritic cells, while maintaining the same T cell immunomodulatory capacity as unstimulated MSCs. Thus, they decrease T-lymphocytes and NK cell proliferation, inhibit the differentiation and allostimulatory capacity of dendritic cells and promote the differentiation of monocytes with an immunosuppressive profile. In addition, we have shown for the first time that proinflammatory priming reduces the variability between different donors and MSC origins. Finally, the effect on CK-MSC is maintained over time and even after a secondary inflammatory stimulus.Conclusions: Cytokine-priming improves the therapeutic potential of MSCs and reduces inter-donor variability.
publishDate 2025
dc.date.none.fl_str_mv 2025
2025-02-17
2025
2025-02-17
dc.type.none.fl_str_mv journal 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://hdl.handle.net/20.500.14352/133330
url https://hdl.handle.net/20.500.14352/133330
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/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
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv reponame:Docta Complutense
instname:Universidad Complutense de Madrid (UCM)
instname_str Universidad Complutense de Madrid (UCM)
reponame_str Docta Complutense
collection Docta Complutense
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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