Extracellular Vesicles Secreted by Mesenchymal Stromal Cells Exert Opposite Effects to Their Cells of Origin in Murine Sodium Dextran Sulfate-Induced Colitis

Autores
Tolomeo, Anna Maria; Castagliuolo, Ignazio; Piccoli, Martina; Grassi, Michele; Magarotto, Fabio; De Lazzari, Giada; Malvicini, Ricardo; Caicci, Federico; Franzin, Chiara; Scarpa, Melania; Macchi, Veronica; De Caro, Raffaele; Angriman, Imerio; Viola, Antonella; Porzionato, Andrea; Pozzobon, Michela; Muraca, Maurizio
Año de publicación
2021
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Several reports have described a beneficial effect of Mesenchymal Stromal Cells (MSCs) and of their secreted extracellular vesicles (EVs) in mice with experimental colitis. However, the effects of the two treatments have not been thoroughly compared in this model. Here, we compared the effects of MSCs and of MSC-EV administration in mice with colitis induced by dextran sulfate sodium (DSS). Since cytokine conditioning was reported to enhance the immune modulatory activity of MSCs, the cells were kept either under standard culture conditions (naïve, nMSCs) or primed with a cocktail of pro-inflammatory cytokines, including IL1β, IL6 and TNFα (induced, iMSCs). In our experimental conditions, nMSCs and iMSCs administration resulted in both clinical and histological worsening and was associated with pro-inflammatory polarization of intestinal macrophages. However, mice treated with iEVs showed clinico-pathological improvement, decreased intestinal fibrosis and angiogenesis and a striking increase in intestinal expression of Mucin 5ac, suggesting improved epithelial function. Moreover, treatment with iEVs resulted in the polarization of intestinal macrophages towards and anti-inflammatory phenotype and in an increased Treg/Teff ratio at the level of the intestinal lymph node. Collectively, these data confirm that MSCs can behave either as anti- or as pro-inflammatory agents depending on the host environment. In contrast, EVs showed a beneficial effect, suggesting a more predictable behavior, a safer therapeutic profile and a higher therapeutic efficacy with respect to their cells of origin.
Fil: Tolomeo, Anna Maria. Fondazione Istituto di Ricerca Pediatrica Città della Speranza; Italia. Università di Padova; Italia. Consorzio per la Ricerca Sanitaria; Italia
Fil: Castagliuolo, Ignazio. Università di Padova; Italia
Fil: Piccoli, Martina. Fondazione Istituto di Ricerca Pediatrica Città della Speranza; Italia
Fil: Grassi, Michele. Università di Padova; Italia
Fil: Magarotto, Fabio. Fondazione Istituto di Ricerca Pediatrica Città della Speranza; Italia. Università di Padova; Italia
Fil: De Lazzari, Giada. Fondazione Istituto di Ricerca Pediatrica Città della Speranza; Italia. Consorzio per la Ricerca Sanitaria; Italia. Università di Padova; Italia
Fil: Malvicini, Ricardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; Argentina. Consorzio per la Ricerca Sanitaria; Italia. Fondazione Istituto di Ricerca Pediatrica Città della Speranza; Italia
Fil: Caicci, Federico. Università di Padova; Italia
Fil: Franzin, Chiara. Fondazione Istituto di Ricerca Pediatrica Città della Speranza; Italia
Fil: Scarpa, Melania. Veneto Institute of Oncology; Italia
Fil: Macchi, Veronica. Università di Padova; Italia
Fil: De Caro, Raffaele. Università di Padova; Italia. Consorzio Per la Ricerca Sanitaria; Italia
Fil: Angriman, Imerio. Università di Padova; Italia
Fil: Viola, Antonella. Università di Padova; Italia
Fil: Porzionato, Andrea. Consorzio Per la Ricerca Sanitaria; Italia. Università di Padova; Italia
Fil: Pozzobon, Michela. Fondazione Istituto Di Ricerca Pediatrica Città Della Speranza; Italia. Università di Padova; Italia
Fil: Muraca, Maurizio. Università di Padova; Italia. Consorzio Per la Ricerca Sanitaria; Italia. Fondazione Istituto Di Ricerca Pediatrica Città Della Speranza; Italia
Materia
EXTRACELLULAR VESICLES
IMMUNOMODULATION
INFLAMMATORY BOWEL DISEASE
MACROPHAGE POLARIZATION
MESENCHYMAL STROMAL CELLS
SODIUM DEXTRAN SULFATE
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/182298
Acceder
id CONICETDig_f34804258b2030253f3ffd3dc7a6a688
oai_identifier_str oai:ri.conicet.gov.ar:11336/182298
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Extracellular Vesicles Secreted by Mesenchymal Stromal Cells Exert Opposite Effects to Their Cells of Origin in Murine Sodium Dextran Sulfate-Induced ColitisTolomeo, Anna MariaCastagliuolo, IgnazioPiccoli, MartinaGrassi, MicheleMagarotto, FabioDe Lazzari, GiadaMalvicini, RicardoCaicci, FedericoFranzin, ChiaraScarpa, MelaniaMacchi, VeronicaDe Caro, RaffaeleAngriman, ImerioViola, AntonellaPorzionato, AndreaPozzobon, MichelaMuraca, MaurizioEXTRACELLULAR VESICLESIMMUNOMODULATIONINFLAMMATORY BOWEL DISEASEMACROPHAGE POLARIZATIONMESENCHYMAL STROMAL CELLSSODIUM DEXTRAN SULFATEhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Several reports have described a beneficial effect of Mesenchymal Stromal Cells (MSCs) and of their secreted extracellular vesicles (EVs) in mice with experimental colitis. However, the effects of the two treatments have not been thoroughly compared in this model. Here, we compared the effects of MSCs and of MSC-EV administration in mice with colitis induced by dextran sulfate sodium (DSS). Since cytokine conditioning was reported to enhance the immune modulatory activity of MSCs, the cells were kept either under standard culture conditions (naïve, nMSCs) or primed with a cocktail of pro-inflammatory cytokines, including IL1β, IL6 and TNFα (induced, iMSCs). In our experimental conditions, nMSCs and iMSCs administration resulted in both clinical and histological worsening and was associated with pro-inflammatory polarization of intestinal macrophages. However, mice treated with iEVs showed clinico-pathological improvement, decreased intestinal fibrosis and angiogenesis and a striking increase in intestinal expression of Mucin 5ac, suggesting improved epithelial function. Moreover, treatment with iEVs resulted in the polarization of intestinal macrophages towards and anti-inflammatory phenotype and in an increased Treg/Teff ratio at the level of the intestinal lymph node. Collectively, these data confirm that MSCs can behave either as anti- or as pro-inflammatory agents depending on the host environment. In contrast, EVs showed a beneficial effect, suggesting a more predictable behavior, a safer therapeutic profile and a higher therapeutic efficacy with respect to their cells of origin.Fil: Tolomeo, Anna Maria. Fondazione Istituto di Ricerca Pediatrica Città della Speranza; Italia. Università di Padova; Italia. Consorzio per la Ricerca Sanitaria; ItaliaFil: Castagliuolo, Ignazio. Università di Padova; ItaliaFil: Piccoli, Martina. Fondazione Istituto di Ricerca Pediatrica Città della Speranza; ItaliaFil: Grassi, Michele. Università di Padova; ItaliaFil: Magarotto, Fabio. Fondazione Istituto di Ricerca Pediatrica Città della Speranza; Italia. Università di Padova; ItaliaFil: De Lazzari, Giada. Fondazione Istituto di Ricerca Pediatrica Città della Speranza; Italia. Consorzio per la Ricerca Sanitaria; Italia. Università di Padova; ItaliaFil: Malvicini, Ricardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; Argentina. Consorzio per la Ricerca Sanitaria; Italia. Fondazione Istituto di Ricerca Pediatrica Città della Speranza; ItaliaFil: Caicci, Federico. Università di Padova; ItaliaFil: Franzin, Chiara. Fondazione Istituto di Ricerca Pediatrica Città della Speranza; ItaliaFil: Scarpa, Melania. Veneto Institute of Oncology; ItaliaFil: Macchi, Veronica. Università di Padova; ItaliaFil: De Caro, Raffaele. Università di Padova; Italia. Consorzio Per la Ricerca Sanitaria; ItaliaFil: Angriman, Imerio. Università di Padova; ItaliaFil: Viola, Antonella. Università di Padova; ItaliaFil: Porzionato, Andrea. Consorzio Per la Ricerca Sanitaria; Italia. Università di Padova; ItaliaFil: Pozzobon, Michela. Fondazione Istituto Di Ricerca Pediatrica Città Della Speranza; Italia. Università di Padova; ItaliaFil: Muraca, Maurizio. Università di Padova; Italia. Consorzio Per la Ricerca Sanitaria; Italia. Fondazione Istituto Di Ricerca Pediatrica Città Della Speranza; ItaliaFrontiers Media2021-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/182298Tolomeo, Anna Maria; Castagliuolo, Ignazio; Piccoli, Martina; Grassi, Michele; Magarotto, Fabio; et al.; Extracellular Vesicles Secreted by Mesenchymal Stromal Cells Exert Opposite Effects to Their Cells of Origin in Murine Sodium Dextran Sulfate-Induced Colitis; Frontiers Media; Frontiers in Immunology; 12; 627605; 4-2021; 1-151664-3224CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.3389/fimmu.2021.627605info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fimmu.2021.627605/fullinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:52:47Zoai:ri.conicet.gov.ar:11336/182298instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:52:47.919CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Extracellular Vesicles Secreted by Mesenchymal Stromal Cells Exert Opposite Effects to Their Cells of Origin in Murine Sodium Dextran Sulfate-Induced Colitis
title Extracellular Vesicles Secreted by Mesenchymal Stromal Cells Exert Opposite Effects to Their Cells of Origin in Murine Sodium Dextran Sulfate-Induced Colitis
spellingShingle Extracellular Vesicles Secreted by Mesenchymal Stromal Cells Exert Opposite Effects to Their Cells of Origin in Murine Sodium Dextran Sulfate-Induced Colitis
Tolomeo, Anna Maria
EXTRACELLULAR VESICLES
IMMUNOMODULATION
INFLAMMATORY BOWEL DISEASE
MACROPHAGE POLARIZATION
MESENCHYMAL STROMAL CELLS
SODIUM DEXTRAN SULFATE
title_short Extracellular Vesicles Secreted by Mesenchymal Stromal Cells Exert Opposite Effects to Their Cells of Origin in Murine Sodium Dextran Sulfate-Induced Colitis
title_full Extracellular Vesicles Secreted by Mesenchymal Stromal Cells Exert Opposite Effects to Their Cells of Origin in Murine Sodium Dextran Sulfate-Induced Colitis
title_fullStr Extracellular Vesicles Secreted by Mesenchymal Stromal Cells Exert Opposite Effects to Their Cells of Origin in Murine Sodium Dextran Sulfate-Induced Colitis
title_full_unstemmed Extracellular Vesicles Secreted by Mesenchymal Stromal Cells Exert Opposite Effects to Their Cells of Origin in Murine Sodium Dextran Sulfate-Induced Colitis
title_sort Extracellular Vesicles Secreted by Mesenchymal Stromal Cells Exert Opposite Effects to Their Cells of Origin in Murine Sodium Dextran Sulfate-Induced Colitis
dc.creator.none.fl_str_mv Tolomeo, Anna Maria
Castagliuolo, Ignazio
Piccoli, Martina
Grassi, Michele
Magarotto, Fabio
De Lazzari, Giada
Malvicini, Ricardo
Caicci, Federico
Franzin, Chiara
Scarpa, Melania
Macchi, Veronica
De Caro, Raffaele
Angriman, Imerio
Viola, Antonella
Porzionato, Andrea
Pozzobon, Michela
Muraca, Maurizio
author Tolomeo, Anna Maria
author_facet Tolomeo, Anna Maria
Castagliuolo, Ignazio
Piccoli, Martina
Grassi, Michele
Magarotto, Fabio
De Lazzari, Giada
Malvicini, Ricardo
Caicci, Federico
Franzin, Chiara
Scarpa, Melania
Macchi, Veronica
De Caro, Raffaele
Angriman, Imerio
Viola, Antonella
Porzionato, Andrea
Pozzobon, Michela
Muraca, Maurizio
author_role author
author2 Castagliuolo, Ignazio
Piccoli, Martina
Grassi, Michele
Magarotto, Fabio
De Lazzari, Giada
Malvicini, Ricardo
Caicci, Federico
Franzin, Chiara
Scarpa, Melania
Macchi, Veronica
De Caro, Raffaele
Angriman, Imerio
Viola, Antonella
Porzionato, Andrea
Pozzobon, Michela
Muraca, Maurizio
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv EXTRACELLULAR VESICLES
IMMUNOMODULATION
INFLAMMATORY BOWEL DISEASE
MACROPHAGE POLARIZATION
MESENCHYMAL STROMAL CELLS
SODIUM DEXTRAN SULFATE
topic EXTRACELLULAR VESICLES
IMMUNOMODULATION
INFLAMMATORY BOWEL DISEASE
MACROPHAGE POLARIZATION
MESENCHYMAL STROMAL CELLS
SODIUM DEXTRAN SULFATE
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Several reports have described a beneficial effect of Mesenchymal Stromal Cells (MSCs) and of their secreted extracellular vesicles (EVs) in mice with experimental colitis. However, the effects of the two treatments have not been thoroughly compared in this model. Here, we compared the effects of MSCs and of MSC-EV administration in mice with colitis induced by dextran sulfate sodium (DSS). Since cytokine conditioning was reported to enhance the immune modulatory activity of MSCs, the cells were kept either under standard culture conditions (naïve, nMSCs) or primed with a cocktail of pro-inflammatory cytokines, including IL1β, IL6 and TNFα (induced, iMSCs). In our experimental conditions, nMSCs and iMSCs administration resulted in both clinical and histological worsening and was associated with pro-inflammatory polarization of intestinal macrophages. However, mice treated with iEVs showed clinico-pathological improvement, decreased intestinal fibrosis and angiogenesis and a striking increase in intestinal expression of Mucin 5ac, suggesting improved epithelial function. Moreover, treatment with iEVs resulted in the polarization of intestinal macrophages towards and anti-inflammatory phenotype and in an increased Treg/Teff ratio at the level of the intestinal lymph node. Collectively, these data confirm that MSCs can behave either as anti- or as pro-inflammatory agents depending on the host environment. In contrast, EVs showed a beneficial effect, suggesting a more predictable behavior, a safer therapeutic profile and a higher therapeutic efficacy with respect to their cells of origin.
Fil: Tolomeo, Anna Maria. Fondazione Istituto di Ricerca Pediatrica Città della Speranza; Italia. Università di Padova; Italia. Consorzio per la Ricerca Sanitaria; Italia
Fil: Castagliuolo, Ignazio. Università di Padova; Italia
Fil: Piccoli, Martina. Fondazione Istituto di Ricerca Pediatrica Città della Speranza; Italia
Fil: Grassi, Michele. Università di Padova; Italia
Fil: Magarotto, Fabio. Fondazione Istituto di Ricerca Pediatrica Città della Speranza; Italia. Università di Padova; Italia
Fil: De Lazzari, Giada. Fondazione Istituto di Ricerca Pediatrica Città della Speranza; Italia. Consorzio per la Ricerca Sanitaria; Italia. Università di Padova; Italia
Fil: Malvicini, Ricardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; Argentina. Consorzio per la Ricerca Sanitaria; Italia. Fondazione Istituto di Ricerca Pediatrica Città della Speranza; Italia
Fil: Caicci, Federico. Università di Padova; Italia
Fil: Franzin, Chiara. Fondazione Istituto di Ricerca Pediatrica Città della Speranza; Italia
Fil: Scarpa, Melania. Veneto Institute of Oncology; Italia
Fil: Macchi, Veronica. Università di Padova; Italia
Fil: De Caro, Raffaele. Università di Padova; Italia. Consorzio Per la Ricerca Sanitaria; Italia
Fil: Angriman, Imerio. Università di Padova; Italia
Fil: Viola, Antonella. Università di Padova; Italia
Fil: Porzionato, Andrea. Consorzio Per la Ricerca Sanitaria; Italia. Università di Padova; Italia
Fil: Pozzobon, Michela. Fondazione Istituto Di Ricerca Pediatrica Città Della Speranza; Italia. Università di Padova; Italia
Fil: Muraca, Maurizio. Università di Padova; Italia. Consorzio Per la Ricerca Sanitaria; Italia. Fondazione Istituto Di Ricerca Pediatrica Città Della Speranza; Italia
description Several reports have described a beneficial effect of Mesenchymal Stromal Cells (MSCs) and of their secreted extracellular vesicles (EVs) in mice with experimental colitis. However, the effects of the two treatments have not been thoroughly compared in this model. Here, we compared the effects of MSCs and of MSC-EV administration in mice with colitis induced by dextran sulfate sodium (DSS). Since cytokine conditioning was reported to enhance the immune modulatory activity of MSCs, the cells were kept either under standard culture conditions (naïve, nMSCs) or primed with a cocktail of pro-inflammatory cytokines, including IL1β, IL6 and TNFα (induced, iMSCs). In our experimental conditions, nMSCs and iMSCs administration resulted in both clinical and histological worsening and was associated with pro-inflammatory polarization of intestinal macrophages. However, mice treated with iEVs showed clinico-pathological improvement, decreased intestinal fibrosis and angiogenesis and a striking increase in intestinal expression of Mucin 5ac, suggesting improved epithelial function. Moreover, treatment with iEVs resulted in the polarization of intestinal macrophages towards and anti-inflammatory phenotype and in an increased Treg/Teff ratio at the level of the intestinal lymph node. Collectively, these data confirm that MSCs can behave either as anti- or as pro-inflammatory agents depending on the host environment. In contrast, EVs showed a beneficial effect, suggesting a more predictable behavior, a safer therapeutic profile and a higher therapeutic efficacy with respect to their cells of origin.
publishDate 2021
dc.date.none.fl_str_mv 2021-04
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/182298
Tolomeo, Anna Maria; Castagliuolo, Ignazio; Piccoli, Martina; Grassi, Michele; Magarotto, Fabio; et al.; Extracellular Vesicles Secreted by Mesenchymal Stromal Cells Exert Opposite Effects to Their Cells of Origin in Murine Sodium Dextran Sulfate-Induced Colitis; Frontiers Media; Frontiers in Immunology; 12; 627605; 4-2021; 1-15
1664-3224
CONICET Digital
CONICET
url http://hdl.handle.net/11336/182298
identifier_str_mv Tolomeo, Anna Maria; Castagliuolo, Ignazio; Piccoli, Martina; Grassi, Michele; Magarotto, Fabio; et al.; Extracellular Vesicles Secreted by Mesenchymal Stromal Cells Exert Opposite Effects to Their Cells of Origin in Murine Sodium Dextran Sulfate-Induced Colitis; Frontiers Media; Frontiers in Immunology; 12; 627605; 4-2021; 1-15
1664-3224
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.3389/fimmu.2021.627605
info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fimmu.2021.627605/full
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1842269182803050496
score 13.13397

Publicaciones similares