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

Background: 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...

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Autores: Areny-Balagueró, A, Camprubí-Rimblas, M, Campaña-Duel, E, Solé-Porta, A, Ceccato, A, Roig, A, Laffey, JG, Closa, D, Artigas, A
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Institut d'Investigació i Innovació Parc Taulí (I3PT)
Repositorio:r-I3PT. Repositorio Institucional Producción Científica del Institut d'Investigació i Innovació Parc Taulí
OAI Identifier:oai:i3pt.fundanetsuite.com:p5311
Acceso en línea:https://i3pt.portalinvestigacion.com/publicaciones/5311
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85207679462&doi=10.3390%2fpharmaceutics16101316&partnerID=40&md5=4c97dfcf1790100654421b21db3a2ae8
Access Level:acceso abierto
Palabra clave:acute lung injury
mesenchymal stem cells
extracellular vesicles
LPS priming
immunomodulation
regeneration
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spelling Priming Mesenchymal Stem Cells with Lipopolysaccharide Boosts the Immunomodulatory and Regenerative Activity of Secreted Extracellular VesiclesAreny-Balagueró, ACamprubí-Rimblas, MCampaña-Duel, ESolé-Porta, ACeccato, ARoig, ALaffey, JGClosa, DArtigas, Aacute lung injurymesenchymal stem cellsextracellular vesiclesLPS primingimmunomodulationregenerationBackground: 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 x 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.MDPI2024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://i3pt.portalinvestigacion.com/publicaciones/5311https://www.scopus.com/inward/record.uri?eid=2-s2.0-85207679462&doi=10.3390%2fpharmaceutics16101316&partnerID=40&md5=4c97dfcf1790100654421b21db3a2ae8PharmaceuticsISSN: 19994923reponame:r-I3PT. Repositorio Institucional Producción Científica del Institut d'Investigació i Innovació Parc Taulíinstname:Institut d'Investigació i Innovació Parc Taulí (I3PT)Inglésinfo:eu-repo/semantics/openAccessoai:i3pt.fundanetsuite.com:p53112026-06-21T15:30:37Z
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, A
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, A
Camprubí-Rimblas, M
Campaña-Duel, E
Solé-Porta, A
Ceccato, A
Roig, A
Laffey, JG
Closa, D
Artigas, A
author Areny-Balagueró, A
author_facet Areny-Balagueró, A
Camprubí-Rimblas, M
Campaña-Duel, E
Solé-Porta, A
Ceccato, A
Roig, A
Laffey, JG
Closa, D
Artigas, A
author_role author
author2 Camprubí-Rimblas, M
Campaña-Duel, E
Solé-Porta, A
Ceccato, A
Roig, A
Laffey, JG
Closa, D
Artigas, A
author2_role author
author
author
author
author
author
author
author
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 Background: 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 x 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
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://i3pt.portalinvestigacion.com/publicaciones/5311
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85207679462&doi=10.3390%2fpharmaceutics16101316&partnerID=40&md5=4c97dfcf1790100654421b21db3a2ae8
url https://i3pt.portalinvestigacion.com/publicaciones/5311
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85207679462&doi=10.3390%2fpharmaceutics16101316&partnerID=40&md5=4c97dfcf1790100654421b21db3a2ae8
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv Pharmaceutics
ISSN: 19994923
reponame:r-I3PT. Repositorio Institucional Producción Científica del Institut d'Investigació i Innovació Parc Taulí
instname:Institut d'Investigació i Innovació Parc Taulí (I3PT)
instname_str Institut d'Investigació i Innovació Parc Taulí (I3PT)
reponame_str r-I3PT. Repositorio Institucional Producción Científica del Institut d'Investigació i Innovació Parc Taulí
collection r-I3PT. Repositorio Institucional Producción Científica del Institut d'Investigació i Innovació Parc Taulí
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