Biodistribution of Intratracheal, Intranasal, and Intravenous Injections of Human Mesenchymal Stromal Cell-Derived Extracellular Vesicles in a Mouse Model for Drug Delivery Studies

Autores
Tolomeo, Anna Maria; Zuccolotto, Gaia; Malvicini, Ricardo; De Lazzari, Giada; Penna, Alessandro; Franco, Chiara; Caicci, Federico; Magarotto, Fabio; Quarta, Santina; Pozzobon, Michela; Rosato, Antonio; Muraca, Maurizio; Collino, Federica
Año de publicación
2023
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) are extensively studied as therapeutic tools. Evaluation of their biodistribution is fundamental to understanding MSC-EVs’ impact on target organs. In our work, MSC-EVs were initially labeled with DiR, a fluorescent lipophilic dye, and administered to BALB/c mice (2.00 × 1010 EV/mice) through the following routes: intravenous (IV), intratracheal (IT) and intranasal (IN). DiR-labeled MSC-EVs were monitored immediately after injection, and after 3 and 24 hours (h). Whole-body analysis, 3 h after IV injection, showed an accumulation of MSC-EVs in the mice abdominal region, compared to IT and IN, where EVs mainly localized at the levels of the chest and brain region, respectively. After 24 h, EV-injected mice retained a stronger positivity in the same regions identified after 3 h from injection. The analyses of isolated organs confirmed the accumulation of EVs in the spleen and liver after IV administration. Twenty-four hours after the IT injection of MSC-EVs, a stronger positivity was detected selectively in the isolated lungs, while for IN, the signal was confined to the brain. In conclusion, these results show that local administration of EVs can increase their concentration in selective organs, limiting their systemic biodistribution and possibly the extra-organ effects. Biodistribution studies can help in the selection of the most appropriate way of administration of MSC-EVs for the treatment of different diseases.
Fil: Tolomeo, Anna Maria. Università di Padova; Italia
Fil: Zuccolotto, Gaia. 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
Fil: De Lazzari, Giada. Università di Padova; Italia
Fil: Penna, Alessandro. Università di Padova; Italia
Fil: Franco, Chiara. Università di Padova; Italia
Fil: Caicci, Federico. Università di Padova; Italia
Fil: Magarotto, Fabio. Università di Padova; Italia
Fil: Quarta, Santina. Università di Padova; Italia
Fil: Pozzobon, Michela. Università di Padova; Italia
Fil: Rosato, Antonio. Università di Padova; Italia
Fil: Muraca, Maurizio. Università di Padova; Italia
Fil: Collino, Federica. Università di Padova; Italia
Materia
BIODISTRIBUTION
DRUG DELIVERY
EXTRACELLULAR VESICLES
PHARMACOKINETICS
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:11336/227755
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/227755
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Biodistribution of Intratracheal, Intranasal, and Intravenous Injections of Human Mesenchymal Stromal Cell-Derived Extracellular Vesicles in a Mouse Model for Drug Delivery StudiesTolomeo, Anna MariaZuccolotto, GaiaMalvicini, RicardoDe Lazzari, GiadaPenna, AlessandroFranco, ChiaraCaicci, FedericoMagarotto, FabioQuarta, SantinaPozzobon, MichelaRosato, AntonioMuraca, MaurizioCollino, FedericaBIODISTRIBUTIONDRUG DELIVERYEXTRACELLULAR VESICLESPHARMACOKINETICShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) are extensively studied as therapeutic tools. Evaluation of their biodistribution is fundamental to understanding MSC-EVs’ impact on target organs. In our work, MSC-EVs were initially labeled with DiR, a fluorescent lipophilic dye, and administered to BALB/c mice (2.00 × 1010 EV/mice) through the following routes: intravenous (IV), intratracheal (IT) and intranasal (IN). DiR-labeled MSC-EVs were monitored immediately after injection, and after 3 and 24 hours (h). Whole-body analysis, 3 h after IV injection, showed an accumulation of MSC-EVs in the mice abdominal region, compared to IT and IN, where EVs mainly localized at the levels of the chest and brain region, respectively. After 24 h, EV-injected mice retained a stronger positivity in the same regions identified after 3 h from injection. The analyses of isolated organs confirmed the accumulation of EVs in the spleen and liver after IV administration. Twenty-four hours after the IT injection of MSC-EVs, a stronger positivity was detected selectively in the isolated lungs, while for IN, the signal was confined to the brain. In conclusion, these results show that local administration of EVs can increase their concentration in selective organs, limiting their systemic biodistribution and possibly the extra-organ effects. Biodistribution studies can help in the selection of the most appropriate way of administration of MSC-EVs for the treatment of different diseases.Fil: Tolomeo, Anna Maria. Università di Padova; ItaliaFil: Zuccolotto, Gaia. 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; ArgentinaFil: De Lazzari, Giada. Università di Padova; ItaliaFil: Penna, Alessandro. Università di Padova; ItaliaFil: Franco, Chiara. Università di Padova; ItaliaFil: Caicci, Federico. Università di Padova; ItaliaFil: Magarotto, Fabio. Università di Padova; ItaliaFil: Quarta, Santina. Università di Padova; ItaliaFil: Pozzobon, Michela. Università di Padova; ItaliaFil: Rosato, Antonio. Università di Padova; ItaliaFil: Muraca, Maurizio. Università di Padova; ItaliaFil: Collino, Federica. Università di Padova; ItaliaMDPI2023-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/227755Tolomeo, Anna Maria; Zuccolotto, Gaia; Malvicini, Ricardo; De Lazzari, Giada; Penna, Alessandro; et al.; Biodistribution of Intratracheal, Intranasal, and Intravenous Injections of Human Mesenchymal Stromal Cell-Derived Extracellular Vesicles in a Mouse Model for Drug Delivery Studies; MDPI; Pharmaceutics; 15; 2; 2-2023; 1-131999-4923CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/1999-4923/15/2/548info:eu-repo/semantics/altIdentifier/doi/10.3390/pharmaceutics15020548info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:44:05Zoai:ri.conicet.gov.ar:11336/227755instacron: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 09:44:05.418CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Biodistribution of Intratracheal, Intranasal, and Intravenous Injections of Human Mesenchymal Stromal Cell-Derived Extracellular Vesicles in a Mouse Model for Drug Delivery Studies
title Biodistribution of Intratracheal, Intranasal, and Intravenous Injections of Human Mesenchymal Stromal Cell-Derived Extracellular Vesicles in a Mouse Model for Drug Delivery Studies
spellingShingle Biodistribution of Intratracheal, Intranasal, and Intravenous Injections of Human Mesenchymal Stromal Cell-Derived Extracellular Vesicles in a Mouse Model for Drug Delivery Studies
Tolomeo, Anna Maria
BIODISTRIBUTION
DRUG DELIVERY
EXTRACELLULAR VESICLES
PHARMACOKINETICS
title_short Biodistribution of Intratracheal, Intranasal, and Intravenous Injections of Human Mesenchymal Stromal Cell-Derived Extracellular Vesicles in a Mouse Model for Drug Delivery Studies
title_full Biodistribution of Intratracheal, Intranasal, and Intravenous Injections of Human Mesenchymal Stromal Cell-Derived Extracellular Vesicles in a Mouse Model for Drug Delivery Studies
title_fullStr Biodistribution of Intratracheal, Intranasal, and Intravenous Injections of Human Mesenchymal Stromal Cell-Derived Extracellular Vesicles in a Mouse Model for Drug Delivery Studies
title_full_unstemmed Biodistribution of Intratracheal, Intranasal, and Intravenous Injections of Human Mesenchymal Stromal Cell-Derived Extracellular Vesicles in a Mouse Model for Drug Delivery Studies
title_sort Biodistribution of Intratracheal, Intranasal, and Intravenous Injections of Human Mesenchymal Stromal Cell-Derived Extracellular Vesicles in a Mouse Model for Drug Delivery Studies
dc.creator.none.fl_str_mv Tolomeo, Anna Maria
Zuccolotto, Gaia
Malvicini, Ricardo
De Lazzari, Giada
Penna, Alessandro
Franco, Chiara
Caicci, Federico
Magarotto, Fabio
Quarta, Santina
Pozzobon, Michela
Rosato, Antonio
Muraca, Maurizio
Collino, Federica
author Tolomeo, Anna Maria
author_facet Tolomeo, Anna Maria
Zuccolotto, Gaia
Malvicini, Ricardo
De Lazzari, Giada
Penna, Alessandro
Franco, Chiara
Caicci, Federico
Magarotto, Fabio
Quarta, Santina
Pozzobon, Michela
Rosato, Antonio
Muraca, Maurizio
Collino, Federica
author_role author
author2 Zuccolotto, Gaia
Malvicini, Ricardo
De Lazzari, Giada
Penna, Alessandro
Franco, Chiara
Caicci, Federico
Magarotto, Fabio
Quarta, Santina
Pozzobon, Michela
Rosato, Antonio
Muraca, Maurizio
Collino, Federica
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv BIODISTRIBUTION
DRUG DELIVERY
EXTRACELLULAR VESICLES
PHARMACOKINETICS
topic BIODISTRIBUTION
DRUG DELIVERY
EXTRACELLULAR VESICLES
PHARMACOKINETICS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) are extensively studied as therapeutic tools. Evaluation of their biodistribution is fundamental to understanding MSC-EVs’ impact on target organs. In our work, MSC-EVs were initially labeled with DiR, a fluorescent lipophilic dye, and administered to BALB/c mice (2.00 × 1010 EV/mice) through the following routes: intravenous (IV), intratracheal (IT) and intranasal (IN). DiR-labeled MSC-EVs were monitored immediately after injection, and after 3 and 24 hours (h). Whole-body analysis, 3 h after IV injection, showed an accumulation of MSC-EVs in the mice abdominal region, compared to IT and IN, where EVs mainly localized at the levels of the chest and brain region, respectively. After 24 h, EV-injected mice retained a stronger positivity in the same regions identified after 3 h from injection. The analyses of isolated organs confirmed the accumulation of EVs in the spleen and liver after IV administration. Twenty-four hours after the IT injection of MSC-EVs, a stronger positivity was detected selectively in the isolated lungs, while for IN, the signal was confined to the brain. In conclusion, these results show that local administration of EVs can increase their concentration in selective organs, limiting their systemic biodistribution and possibly the extra-organ effects. Biodistribution studies can help in the selection of the most appropriate way of administration of MSC-EVs for the treatment of different diseases.
Fil: Tolomeo, Anna Maria. Università di Padova; Italia
Fil: Zuccolotto, Gaia. 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
Fil: De Lazzari, Giada. Università di Padova; Italia
Fil: Penna, Alessandro. Università di Padova; Italia
Fil: Franco, Chiara. Università di Padova; Italia
Fil: Caicci, Federico. Università di Padova; Italia
Fil: Magarotto, Fabio. Università di Padova; Italia
Fil: Quarta, Santina. Università di Padova; Italia
Fil: Pozzobon, Michela. Università di Padova; Italia
Fil: Rosato, Antonio. Università di Padova; Italia
Fil: Muraca, Maurizio. Università di Padova; Italia
Fil: Collino, Federica. Università di Padova; Italia
description Mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) are extensively studied as therapeutic tools. Evaluation of their biodistribution is fundamental to understanding MSC-EVs’ impact on target organs. In our work, MSC-EVs were initially labeled with DiR, a fluorescent lipophilic dye, and administered to BALB/c mice (2.00 × 1010 EV/mice) through the following routes: intravenous (IV), intratracheal (IT) and intranasal (IN). DiR-labeled MSC-EVs were monitored immediately after injection, and after 3 and 24 hours (h). Whole-body analysis, 3 h after IV injection, showed an accumulation of MSC-EVs in the mice abdominal region, compared to IT and IN, where EVs mainly localized at the levels of the chest and brain region, respectively. After 24 h, EV-injected mice retained a stronger positivity in the same regions identified after 3 h from injection. The analyses of isolated organs confirmed the accumulation of EVs in the spleen and liver after IV administration. Twenty-four hours after the IT injection of MSC-EVs, a stronger positivity was detected selectively in the isolated lungs, while for IN, the signal was confined to the brain. In conclusion, these results show that local administration of EVs can increase their concentration in selective organs, limiting their systemic biodistribution and possibly the extra-organ effects. Biodistribution studies can help in the selection of the most appropriate way of administration of MSC-EVs for the treatment of different diseases.
publishDate 2023
dc.date.none.fl_str_mv 2023-02
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/11336/227755
Tolomeo, Anna Maria; Zuccolotto, Gaia; Malvicini, Ricardo; De Lazzari, Giada; Penna, Alessandro; et al.; Biodistribution of Intratracheal, Intranasal, and Intravenous Injections of Human Mesenchymal Stromal Cell-Derived Extracellular Vesicles in a Mouse Model for Drug Delivery Studies; MDPI; Pharmaceutics; 15; 2; 2-2023; 1-13
1999-4923
CONICET Digital
CONICET
url http://hdl.handle.net/11336/227755
identifier_str_mv Tolomeo, Anna Maria; Zuccolotto, Gaia; Malvicini, Ricardo; De Lazzari, Giada; Penna, Alessandro; et al.; Biodistribution of Intratracheal, Intranasal, and Intravenous Injections of Human Mesenchymal Stromal Cell-Derived Extracellular Vesicles in a Mouse Model for Drug Delivery Studies; MDPI; Pharmaceutics; 15; 2; 2-2023; 1-13
1999-4923
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/1999-4923/15/2/548
info:eu-repo/semantics/altIdentifier/doi/10.3390/pharmaceutics15020548
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 MDPI
publisher.none.fl_str_mv MDPI
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
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