Mesenchymal stem cell therapy facilitates donor lung preservation by reducing oxidative damage during ischemia

Autores
Pacienza, Natalia; Santa Cruz, Diego Mario; Malvicini, Ricardo; Robledo, Oscar; Lemus Larralde, Gastón; Bertolotti, Alejandro Mario; Marcos, Martín; Yannarelli, Gustavo Gabriel
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Lung transplantation is a lifesaving therapy for people living with severe, life-threatening lung disease. The high mortality rate among patients awaiting transplantation is mainly due to the low percentage of lungs that are deemed acceptable for implantation. Thus, the current shortage of lung donors may be significantly reduced by implementing different therapeutic strategies which facilitate both organ preservation and recovery. Here, we studied whether the anti-inflammatory effect of human umbilical cord-derived mesenchymal stem cells (HUCPVCs) increases lung availability by improving organ preservation. We developed a lung preservation rat model that mimics the different stages by which donor organs must undergo before implantation. The therapeutic schema was as follows: cardiac arrest, warm ischemia (2h at room temperature), cold ischemia (1.5h at 4°C, with Perfadex), and normothermic lung perfusion with ventilation (Steen solution, 1h). After 1h of warm ischemia, HUCPVCs (1x106 cells) or vehicle were infused via the pulmonary artery. Physiologic data (pressure-volume curves) were acquired right after the cardiac arrest and at the end of the perfusion. Interestingly, although lung edema did not change among groups, lung compliance dropped a 34% in the HUCPVCs-treated group, while the vehicle group showed a stronger reduction (69%, p<0.0001). Histologic assessment demonstrated less overall inflammation in HUCPVCs-treated lungs. In addition, MPO activity, a neutrophil marker, was reduced by 41% compared with vehicle (p<0.01). MSCs therapy significantly decreased tissue oxidative damage by controlling reactive oxygen species production. Accordingly, catalase and superoxide dismutase enzyme activities remained at baseline levels. In conclusion, these results demonstrate that the anti-inflammatory effect of MSCs protects donor lungs against ischemic injury and postulate MSCs therapy as a novel tool for organ preservation.
Fil: Pacienza, Natalia. 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: Santa Cruz, Diego Mario. 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: 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: Robledo, Oscar. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina
Fil: Lemus Larralde, Gastón. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina
Fil: Bertolotti, Alejandro Mario. Fundación Favaloro; Argentina
Fil: Marcos, Martín. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina
Fil: Yannarelli, Gustavo Gabriel. 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
Materia
MESENCHYMAL STEM CELL
ORGAN PRESERVATION
LUNG TRANSPLANTATION
CELL THERAPY
INFLAMMATION
OXIDATIVE STRESS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/121400
Acceder
id CONICETDig_0b5cabfce006154d0ec34717ee72129e
oai_identifier_str oai:ri.conicet.gov.ar:11336/121400
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Mesenchymal stem cell therapy facilitates donor lung preservation by reducing oxidative damage during ischemiaPacienza, NataliaSanta Cruz, Diego MarioMalvicini, RicardoRobledo, OscarLemus Larralde, GastónBertolotti, Alejandro MarioMarcos, MartínYannarelli, Gustavo GabrielMESENCHYMAL STEM CELLORGAN PRESERVATIONLUNG TRANSPLANTATIONCELL THERAPYINFLAMMATIONOXIDATIVE STRESShttps://purl.org/becyt/ford/3.4https://purl.org/becyt/ford/3Lung transplantation is a lifesaving therapy for people living with severe, life-threatening lung disease. The high mortality rate among patients awaiting transplantation is mainly due to the low percentage of lungs that are deemed acceptable for implantation. Thus, the current shortage of lung donors may be significantly reduced by implementing different therapeutic strategies which facilitate both organ preservation and recovery. Here, we studied whether the anti-inflammatory effect of human umbilical cord-derived mesenchymal stem cells (HUCPVCs) increases lung availability by improving organ preservation. We developed a lung preservation rat model that mimics the different stages by which donor organs must undergo before implantation. The therapeutic schema was as follows: cardiac arrest, warm ischemia (2h at room temperature), cold ischemia (1.5h at 4°C, with Perfadex), and normothermic lung perfusion with ventilation (Steen solution, 1h). After 1h of warm ischemia, HUCPVCs (1x106 cells) or vehicle were infused via the pulmonary artery. Physiologic data (pressure-volume curves) were acquired right after the cardiac arrest and at the end of the perfusion. Interestingly, although lung edema did not change among groups, lung compliance dropped a 34% in the HUCPVCs-treated group, while the vehicle group showed a stronger reduction (69%, p<0.0001). Histologic assessment demonstrated less overall inflammation in HUCPVCs-treated lungs. In addition, MPO activity, a neutrophil marker, was reduced by 41% compared with vehicle (p<0.01). MSCs therapy significantly decreased tissue oxidative damage by controlling reactive oxygen species production. Accordingly, catalase and superoxide dismutase enzyme activities remained at baseline levels. In conclusion, these results demonstrate that the anti-inflammatory effect of MSCs protects donor lungs against ischemic injury and postulate MSCs therapy as a novel tool for organ preservation.Fil: Pacienza, Natalia. 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: Santa Cruz, Diego Mario. 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: 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: Robledo, Oscar. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; ArgentinaFil: Lemus Larralde, Gastón. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; ArgentinaFil: Bertolotti, Alejandro Mario. Fundación Favaloro; ArgentinaFil: Marcos, Martín. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; ArgentinaFil: Yannarelli, Gustavo Gabriel. 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; ArgentinaHindawi Publishing Corporation2019-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/121400Pacienza, Natalia; Santa Cruz, Diego Mario; Malvicini, Ricardo; Robledo, Oscar; Lemus Larralde, Gastón; et al.; Mesenchymal stem cell therapy facilitates donor lung preservation by reducing oxidative damage during ischemia; Hindawi Publishing Corporation; Stem Cells International; 2019; 8-2019; 1-141687-9678CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.hindawi.com/journals/sci/info:eu-repo/semantics/altIdentifier/doi/10.1155/2019/8089215info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:08:52Zoai:ri.conicet.gov.ar:11336/121400instacron: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:34982025-09-29 10:08:52.947CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Mesenchymal stem cell therapy facilitates donor lung preservation by reducing oxidative damage during ischemia
title Mesenchymal stem cell therapy facilitates donor lung preservation by reducing oxidative damage during ischemia
spellingShingle Mesenchymal stem cell therapy facilitates donor lung preservation by reducing oxidative damage during ischemia
Pacienza, Natalia
MESENCHYMAL STEM CELL
ORGAN PRESERVATION
LUNG TRANSPLANTATION
CELL THERAPY
INFLAMMATION
OXIDATIVE STRESS
title_short Mesenchymal stem cell therapy facilitates donor lung preservation by reducing oxidative damage during ischemia
title_full Mesenchymal stem cell therapy facilitates donor lung preservation by reducing oxidative damage during ischemia
title_fullStr Mesenchymal stem cell therapy facilitates donor lung preservation by reducing oxidative damage during ischemia
title_full_unstemmed Mesenchymal stem cell therapy facilitates donor lung preservation by reducing oxidative damage during ischemia
title_sort Mesenchymal stem cell therapy facilitates donor lung preservation by reducing oxidative damage during ischemia
dc.creator.none.fl_str_mv Pacienza, Natalia
Santa Cruz, Diego Mario
Malvicini, Ricardo
Robledo, Oscar
Lemus Larralde, Gastón
Bertolotti, Alejandro Mario
Marcos, Martín
Yannarelli, Gustavo Gabriel
author Pacienza, Natalia
author_facet Pacienza, Natalia
Santa Cruz, Diego Mario
Malvicini, Ricardo
Robledo, Oscar
Lemus Larralde, Gastón
Bertolotti, Alejandro Mario
Marcos, Martín
Yannarelli, Gustavo Gabriel
author_role author
author2 Santa Cruz, Diego Mario
Malvicini, Ricardo
Robledo, Oscar
Lemus Larralde, Gastón
Bertolotti, Alejandro Mario
Marcos, Martín
Yannarelli, Gustavo Gabriel
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv MESENCHYMAL STEM CELL
ORGAN PRESERVATION
LUNG TRANSPLANTATION
CELL THERAPY
INFLAMMATION
OXIDATIVE STRESS
topic MESENCHYMAL STEM CELL
ORGAN PRESERVATION
LUNG TRANSPLANTATION
CELL THERAPY
INFLAMMATION
OXIDATIVE STRESS
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.4
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Lung transplantation is a lifesaving therapy for people living with severe, life-threatening lung disease. The high mortality rate among patients awaiting transplantation is mainly due to the low percentage of lungs that are deemed acceptable for implantation. Thus, the current shortage of lung donors may be significantly reduced by implementing different therapeutic strategies which facilitate both organ preservation and recovery. Here, we studied whether the anti-inflammatory effect of human umbilical cord-derived mesenchymal stem cells (HUCPVCs) increases lung availability by improving organ preservation. We developed a lung preservation rat model that mimics the different stages by which donor organs must undergo before implantation. The therapeutic schema was as follows: cardiac arrest, warm ischemia (2h at room temperature), cold ischemia (1.5h at 4°C, with Perfadex), and normothermic lung perfusion with ventilation (Steen solution, 1h). After 1h of warm ischemia, HUCPVCs (1x106 cells) or vehicle were infused via the pulmonary artery. Physiologic data (pressure-volume curves) were acquired right after the cardiac arrest and at the end of the perfusion. Interestingly, although lung edema did not change among groups, lung compliance dropped a 34% in the HUCPVCs-treated group, while the vehicle group showed a stronger reduction (69%, p<0.0001). Histologic assessment demonstrated less overall inflammation in HUCPVCs-treated lungs. In addition, MPO activity, a neutrophil marker, was reduced by 41% compared with vehicle (p<0.01). MSCs therapy significantly decreased tissue oxidative damage by controlling reactive oxygen species production. Accordingly, catalase and superoxide dismutase enzyme activities remained at baseline levels. In conclusion, these results demonstrate that the anti-inflammatory effect of MSCs protects donor lungs against ischemic injury and postulate MSCs therapy as a novel tool for organ preservation.
Fil: Pacienza, Natalia. 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: Santa Cruz, Diego Mario. 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: 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: Robledo, Oscar. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina
Fil: Lemus Larralde, Gastón. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina
Fil: Bertolotti, Alejandro Mario. Fundación Favaloro; Argentina
Fil: Marcos, Martín. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina
Fil: Yannarelli, Gustavo Gabriel. 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
description Lung transplantation is a lifesaving therapy for people living with severe, life-threatening lung disease. The high mortality rate among patients awaiting transplantation is mainly due to the low percentage of lungs that are deemed acceptable for implantation. Thus, the current shortage of lung donors may be significantly reduced by implementing different therapeutic strategies which facilitate both organ preservation and recovery. Here, we studied whether the anti-inflammatory effect of human umbilical cord-derived mesenchymal stem cells (HUCPVCs) increases lung availability by improving organ preservation. We developed a lung preservation rat model that mimics the different stages by which donor organs must undergo before implantation. The therapeutic schema was as follows: cardiac arrest, warm ischemia (2h at room temperature), cold ischemia (1.5h at 4°C, with Perfadex), and normothermic lung perfusion with ventilation (Steen solution, 1h). After 1h of warm ischemia, HUCPVCs (1x106 cells) or vehicle were infused via the pulmonary artery. Physiologic data (pressure-volume curves) were acquired right after the cardiac arrest and at the end of the perfusion. Interestingly, although lung edema did not change among groups, lung compliance dropped a 34% in the HUCPVCs-treated group, while the vehicle group showed a stronger reduction (69%, p<0.0001). Histologic assessment demonstrated less overall inflammation in HUCPVCs-treated lungs. In addition, MPO activity, a neutrophil marker, was reduced by 41% compared with vehicle (p<0.01). MSCs therapy significantly decreased tissue oxidative damage by controlling reactive oxygen species production. Accordingly, catalase and superoxide dismutase enzyme activities remained at baseline levels. In conclusion, these results demonstrate that the anti-inflammatory effect of MSCs protects donor lungs against ischemic injury and postulate MSCs therapy as a novel tool for organ preservation.
publishDate 2019
dc.date.none.fl_str_mv 2019-08
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/11336/121400
Pacienza, Natalia; Santa Cruz, Diego Mario; Malvicini, Ricardo; Robledo, Oscar; Lemus Larralde, Gastón; et al.; Mesenchymal stem cell therapy facilitates donor lung preservation by reducing oxidative damage during ischemia; Hindawi Publishing Corporation; Stem Cells International; 2019; 8-2019; 1-14
1687-9678
CONICET Digital
CONICET
url http://hdl.handle.net/11336/121400
identifier_str_mv Pacienza, Natalia; Santa Cruz, Diego Mario; Malvicini, Ricardo; Robledo, Oscar; Lemus Larralde, Gastón; et al.; Mesenchymal stem cell therapy facilitates donor lung preservation by reducing oxidative damage during ischemia; Hindawi Publishing Corporation; Stem Cells International; 2019; 8-2019; 1-14
1687-9678
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.hindawi.com/journals/sci/
info:eu-repo/semantics/altIdentifier/doi/10.1155/2019/8089215
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Hindawi Publishing Corporation
publisher.none.fl_str_mv Hindawi Publishing Corporation
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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score 13.070432

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