Priming Mesenchymal Stem Cells with Lipopolysaccharide Boosts the Immunomodulatory and Regenerative Activity of Secreted Extracellular Vesicles

Mesenchymal stem cells (MSCs)-derived extracellular vesicles (EVs) have been proposed as an alternative to live-cell administration for Acute Respiratory Distress Syndrome (ARDS). MSC-EVs can be chiefly influenced by the environment to which the MSCs are exposed. Here, lipopolysaccharide (LPS) primi...

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Autores: Areny Balagueró, Aina, Camprubí Rimblas, Marta, Campaña-Duel, Elena, Solé Porta, Anna, Ceccato, Adrián, Roig Serra, Anna, Laffey, John G., Closa, Daniel, Artigas, Antonio
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/370780
Acceso en línea:http://hdl.handle.net/10261/370780
Access Level:acceso abierto
Palabra clave:Acute lung injury
Mesenchymal stem cells
Extracellular vesicles
LPS priming
Immunomodulation
Regeneration
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dc.title.none.fl_str_mv Priming Mesenchymal Stem Cells with Lipopolysaccharide Boosts the Immunomodulatory and Regenerative Activity of Secreted Extracellular Vesicles
title Priming Mesenchymal Stem Cells with Lipopolysaccharide Boosts the Immunomodulatory and Regenerative Activity of Secreted Extracellular Vesicles
spellingShingle Priming Mesenchymal Stem Cells with Lipopolysaccharide Boosts the Immunomodulatory and Regenerative Activity of Secreted Extracellular Vesicles
Areny Balagueró, Aina
Acute lung injury
Mesenchymal stem cells
Extracellular vesicles
LPS priming
Immunomodulation
Regeneration
title_short Priming Mesenchymal Stem Cells with Lipopolysaccharide Boosts the Immunomodulatory and Regenerative Activity of Secreted Extracellular Vesicles
title_full Priming Mesenchymal Stem Cells with Lipopolysaccharide Boosts the Immunomodulatory and Regenerative Activity of Secreted Extracellular Vesicles
title_fullStr Priming Mesenchymal Stem Cells with Lipopolysaccharide Boosts the Immunomodulatory and Regenerative Activity of Secreted Extracellular Vesicles
title_full_unstemmed Priming Mesenchymal Stem Cells with Lipopolysaccharide Boosts the Immunomodulatory and Regenerative Activity of Secreted Extracellular Vesicles
title_sort Priming Mesenchymal Stem Cells with Lipopolysaccharide Boosts the Immunomodulatory and Regenerative Activity of Secreted Extracellular Vesicles
dc.creator.none.fl_str_mv Areny Balagueró, Aina
Camprubí Rimblas, Marta
Campaña-Duel, Elena
Solé Porta, Anna
Ceccato, Adrián
Roig Serra, Anna
Laffey, John G.
Closa, Daniel
Artigas, Antonio
author Areny Balagueró, Aina
author_facet Areny Balagueró, Aina
Camprubí Rimblas, Marta
Campaña-Duel, Elena
Solé Porta, Anna
Ceccato, Adrián
Roig Serra, Anna
Laffey, John G.
Closa, Daniel
Artigas, Antonio
author_role author
author2 Camprubí Rimblas, Marta
Campaña-Duel, Elena
Solé Porta, Anna
Ceccato, Adrián
Roig Serra, Anna
Laffey, John G.
Closa, Daniel
Artigas, Antonio
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Fundación Ramón Areces
Ministerio de Economía y Competitividad (España)
Instituto de Salud Carlos III
European Commission
Institut d'Investigació i Innovació Parc Taulí
European Society of Intensive Care Medicine
Centro de Investigación Biomédica en Red Enfermedades Respiratorias (España)
Generalitat de Catalunya
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Acute lung injury
Mesenchymal stem cells
Extracellular vesicles
LPS priming
Immunomodulation
Regeneration
topic Acute lung injury
Mesenchymal stem cells
Extracellular vesicles
LPS priming
Immunomodulation
Regeneration
description Mesenchymal stem cells (MSCs)-derived extracellular vesicles (EVs) have been proposed as an alternative to live-cell administration for Acute Respiratory Distress Syndrome (ARDS). MSC-EVs can be chiefly influenced by the environment to which the MSCs are exposed. Here, lipopolysaccharide (LPS) priming of MSCs was used as a strategy to boost the natural therapeutic potential of the EVs in acute lung injury (ALI). Methods: The regenerative and immunemodulatory effect of LPS-primed MSC-EVs (LPS-EVs) and non-primed MSC-EVs (C-EVs) were evaluated in vitro on alveolar epithelial cells and macrophage-like THP-1 cells. In vivo, ALI was induced in adult male rats by the intrapulmonary instillation of HCl and LPS. Rats (n = 8 to 22/group) were randomized to receive a single bolus (1 × 108 particles) of LPS-EVs, C-EVs, or saline. Lung injury severity was assessed at 72 h in lung tissue and bronchoalveolar lavage. Results: In vitro, LPS-EVs improved wound regeneration and attenuated the inflammatory response triggered by the P. aeruginosa infection, enhancing the M2 macrophage phenotype. In in vivo studies, LPS-EVs, but not C-EVs, significantly decreased the neutrophilic infiltration and myeloperoxidase (MPO) activity in lung tissue. Alveolar macrophages from LPS-EVs-treated animals exhibited a reduced expression of CXCL-1, a key neutrophil chemoattractant. However, both C-EVs and LPS-EVs reduced alveolar epithelial and endothelial permeability, mitigating lung damage. Conclusions: EVs from LPS-primed MSCs resulted in a better resolution of ALI, achieving a greater balance in neutrophil infiltration and activation, while avoiding the complete disruption of the alveolar barrier. This opens new avenues, paving the way for the clinical implementation of cell-based therapies.
publishDate 2024
dc.date.none.fl_str_mv 2024
2024
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
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dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/370780
url http://hdl.handle.net/10261/370780
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016 (ISCIII)/PI18%2F00677
The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI https://doi.org/10.3390/pharmaceutics16101316
https://doi.org/10.3390/pharmaceutics16101316
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
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spelling Priming Mesenchymal Stem Cells with Lipopolysaccharide Boosts the Immunomodulatory and Regenerative Activity of Secreted Extracellular VesiclesAreny Balagueró, AinaCamprubí Rimblas, MartaCampaña-Duel, ElenaSolé Porta, AnnaCeccato, AdriánRoig Serra, AnnaLaffey, John G.Closa, DanielArtigas, AntonioAcute lung injuryMesenchymal stem cellsExtracellular vesiclesLPS primingImmunomodulationRegenerationMesenchymal stem cells (MSCs)-derived extracellular vesicles (EVs) have been proposed as an alternative to live-cell administration for Acute Respiratory Distress Syndrome (ARDS). MSC-EVs can be chiefly influenced by the environment to which the MSCs are exposed. Here, lipopolysaccharide (LPS) priming of MSCs was used as a strategy to boost the natural therapeutic potential of the EVs in acute lung injury (ALI). Methods: The regenerative and immunemodulatory effect of LPS-primed MSC-EVs (LPS-EVs) and non-primed MSC-EVs (C-EVs) were evaluated in vitro on alveolar epithelial cells and macrophage-like THP-1 cells. In vivo, ALI was induced in adult male rats by the intrapulmonary instillation of HCl and LPS. Rats (n = 8 to 22/group) were randomized to receive a single bolus (1 × 108 particles) of LPS-EVs, C-EVs, or saline. Lung injury severity was assessed at 72 h in lung tissue and bronchoalveolar lavage. Results: In vitro, LPS-EVs improved wound regeneration and attenuated the inflammatory response triggered by the P. aeruginosa infection, enhancing the M2 macrophage phenotype. In in vivo studies, LPS-EVs, but not C-EVs, significantly decreased the neutrophilic infiltration and myeloperoxidase (MPO) activity in lung tissue. Alveolar macrophages from LPS-EVs-treated animals exhibited a reduced expression of CXCL-1, a key neutrophil chemoattractant. However, both C-EVs and LPS-EVs reduced alveolar epithelial and endothelial permeability, mitigating lung damage. Conclusions: EVs from LPS-primed MSCs resulted in a better resolution of ALI, achieving a greater balance in neutrophil infiltration and activation, while avoiding the complete disruption of the alveolar barrier. This opens new avenues, paving the way for the clinical implementation of cell-based therapies.This work was supported by the Fundación Ramón Areces under grant CIVP19S8207; the Ministerio de Economía y Competitividad-Instituto de Salud Carlos III (ISCIII) under grant PI18/00677, Co-funded by the European Regional Development Fund; “A way to make Europe”; the Institut d’Investigació I Innovació Parc Taulí (I3PT) under grants CIR2020/028 and CIR2021/027; the European Society of Intensive Medicine (ESICM) under the Levi-Montalcini Biomedical Sciences Award; the Centro de Investigación Biomedica en Red de Enfermedades Respiratorias (CIBERES); and the Generalitat de Catalunya (2021SGR00446). E.C.-D. and A.S.-P. acknowledge receiving financial support from the Ministerio de Ciencia, Innovación y Universidades (FPU22/00725 and FPU21/04142, respectively); and AC acknowledges receiving financial support from ISCIII (Sara Borrell 2021: CD21/00087). The funding sources had no role in the design and conduct of this study; the collection, management, analysis and interpretation of the data; the preparation, review or approval of the manuscript; or in the decision to submit the manuscript for publication.Peer reviewedMultidisciplinary Digital Publishing InstituteFundación Ramón ArecesMinisterio de Economía y Competitividad (España)Instituto de Salud Carlos IIIEuropean CommissionInstitut d'Investigació i Innovació Parc TaulíEuropean Society of Intensive Care MedicineCentro de Investigación Biomédica en Red Enfermedades Respiratorias (España)Generalitat de CatalunyaConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2024202420242024info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/370780reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016 (ISCIII)/PI18%2F00677The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI https://doi.org/10.3390/pharmaceutics16101316https://doi.org/10.3390/pharmaceutics16101316Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3707802026-05-22T06:33:51Z
score 15.812429

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