Mesenchymal stromal cells improve cardiac function and left ventricular remodeling in a heart transplantation model

Autores
Montanari, Sonia; Dayan, Victor; Yannarelli, Gustavo Gabriel; Billia, Filio; Viswanathan, Sowmya; Connelly, Kim A.; Keating, Armand
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background: Ischemia/reperfusion (I/R) injury is an inevitable consequence of organ transplantation and a major determinant of patient and graft survival in heart transplantation. Bone marrow–mesenchymal stromal cell (BM-MSC) treatment is a potentially effective cell therapy for cardiac disease. We investigated the effects of intravenous delivery of BM-MSCs in the acute phase post-transplant in a heterotopic heart transplantation (HHT) model associated with I/R injury. Methods: Hearts of wild-type Lewis (WT LEW) rats were harvested and transplanted heterotopically into the necks of recipient WT LEW rats. Forty-eight hours after HHT, BM-MSCs were injected intravenously into animals in the experimental group, whereas controls received normal saline (NS). Results: Eight days after BM-MSC injection, fractional shortening of transplanted hearts was significantly higher and left ventricular systolic diameter was lower in the BM-MSC group compared with controls, whereas no differences were found 28 days after infusion. A reduction in ventricular remodeling and cardiac fibrosis was observed by histochemical analysis and confirmed by cardiac magnetic resonance imaging in the BM-MSC group. The perivascular stromal cells’ density and the number of capillaries were increased whereas the number of apoptotic cells decreased significantly in transplanted hearts in the BM-MSC group compared with the NS group. Conclusions: We showed early improvement in cardiac function and subsequent enhanced ventricular remodeling, reduced cardiac fibrosis, augmented neo-vascularization and decreased cardiomyocyte apoptosis of the transplanted heart in a heterotopic transplantation model after intravenous infusion of BM-derived MSCs. Our data suggest that clinical studies with BM-MSCs are warranted to understand their effects on cardiac graft and transplant recipient survival.
Fil: Montanari, Sonia. University Health Network; Canadá. University of Toronto; Canadá
Fil: Dayan, Victor. University Health Network; Canadá
Fil: Yannarelli, Gustavo Gabriel. University Health Network; Canadá. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Billia, Filio. Toronto General Hospital; Canadá
Fil: Viswanathan, Sowmya. University Health Network; Canadá
Fil: Connelly, Kim A.. Keenan Research Centre; Canadá
Fil: Keating, Armand. University Health Network; Canadá. University of Toronto; Canadá
Materia
Mesenchymal Stromal Cells
Heart Transplantation
Remodeling
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/42282
Acceder
id CONICETDig_a2ca0af6a97c5d51bed48c5514118f66
oai_identifier_str oai:ri.conicet.gov.ar:11336/42282
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Mesenchymal stromal cells improve cardiac function and left ventricular remodeling in a heart transplantation modelMontanari, SoniaDayan, VictorYannarelli, Gustavo GabrielBillia, FilioViswanathan, SowmyaConnelly, Kim A.Keating, ArmandMesenchymal Stromal CellsHeart TransplantationRemodelinghttps://purl.org/becyt/ford/3.4https://purl.org/becyt/ford/3Background: Ischemia/reperfusion (I/R) injury is an inevitable consequence of organ transplantation and a major determinant of patient and graft survival in heart transplantation. Bone marrow–mesenchymal stromal cell (BM-MSC) treatment is a potentially effective cell therapy for cardiac disease. We investigated the effects of intravenous delivery of BM-MSCs in the acute phase post-transplant in a heterotopic heart transplantation (HHT) model associated with I/R injury. Methods: Hearts of wild-type Lewis (WT LEW) rats were harvested and transplanted heterotopically into the necks of recipient WT LEW rats. Forty-eight hours after HHT, BM-MSCs were injected intravenously into animals in the experimental group, whereas controls received normal saline (NS). Results: Eight days after BM-MSC injection, fractional shortening of transplanted hearts was significantly higher and left ventricular systolic diameter was lower in the BM-MSC group compared with controls, whereas no differences were found 28 days after infusion. A reduction in ventricular remodeling and cardiac fibrosis was observed by histochemical analysis and confirmed by cardiac magnetic resonance imaging in the BM-MSC group. The perivascular stromal cells’ density and the number of capillaries were increased whereas the number of apoptotic cells decreased significantly in transplanted hearts in the BM-MSC group compared with the NS group. Conclusions: We showed early improvement in cardiac function and subsequent enhanced ventricular remodeling, reduced cardiac fibrosis, augmented neo-vascularization and decreased cardiomyocyte apoptosis of the transplanted heart in a heterotopic transplantation model after intravenous infusion of BM-derived MSCs. Our data suggest that clinical studies with BM-MSCs are warranted to understand their effects on cardiac graft and transplant recipient survival.Fil: Montanari, Sonia. University Health Network; Canadá. University of Toronto; CanadáFil: Dayan, Victor. University Health Network; CanadáFil: Yannarelli, Gustavo Gabriel. University Health Network; Canadá. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Billia, Filio. Toronto General Hospital; CanadáFil: Viswanathan, Sowmya. University Health Network; CanadáFil: Connelly, Kim A.. Keenan Research Centre; CanadáFil: Keating, Armand. University Health Network; Canadá. University of Toronto; CanadáElsevier Science Inc2015-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/42282Montanari, Sonia; Dayan, Victor; Yannarelli, Gustavo Gabriel; Billia, Filio; Viswanathan, Sowmya; et al.; Mesenchymal stromal cells improve cardiac function and left ventricular remodeling in a heart transplantation model; Elsevier Science Inc; Journal of Heart and Lung Transplantation; 34; 11; 11-2015; 1481-14881053-2498CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.healun.2015.05.008info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S1053249815012796info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:46:46Zoai:ri.conicet.gov.ar:11336/42282instacron: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 09:46:47.195CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Mesenchymal stromal cells improve cardiac function and left ventricular remodeling in a heart transplantation model
title Mesenchymal stromal cells improve cardiac function and left ventricular remodeling in a heart transplantation model
spellingShingle Mesenchymal stromal cells improve cardiac function and left ventricular remodeling in a heart transplantation model
Montanari, Sonia
Mesenchymal Stromal Cells
Heart Transplantation
Remodeling
title_short Mesenchymal stromal cells improve cardiac function and left ventricular remodeling in a heart transplantation model
title_full Mesenchymal stromal cells improve cardiac function and left ventricular remodeling in a heart transplantation model
title_fullStr Mesenchymal stromal cells improve cardiac function and left ventricular remodeling in a heart transplantation model
title_full_unstemmed Mesenchymal stromal cells improve cardiac function and left ventricular remodeling in a heart transplantation model
title_sort Mesenchymal stromal cells improve cardiac function and left ventricular remodeling in a heart transplantation model
dc.creator.none.fl_str_mv Montanari, Sonia
Dayan, Victor
Yannarelli, Gustavo Gabriel
Billia, Filio
Viswanathan, Sowmya
Connelly, Kim A.
Keating, Armand
author Montanari, Sonia
author_facet Montanari, Sonia
Dayan, Victor
Yannarelli, Gustavo Gabriel
Billia, Filio
Viswanathan, Sowmya
Connelly, Kim A.
Keating, Armand
author_role author
author2 Dayan, Victor
Yannarelli, Gustavo Gabriel
Billia, Filio
Viswanathan, Sowmya
Connelly, Kim A.
Keating, Armand
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Mesenchymal Stromal Cells
Heart Transplantation
Remodeling
topic Mesenchymal Stromal Cells
Heart Transplantation
Remodeling
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.4
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Background: Ischemia/reperfusion (I/R) injury is an inevitable consequence of organ transplantation and a major determinant of patient and graft survival in heart transplantation. Bone marrow–mesenchymal stromal cell (BM-MSC) treatment is a potentially effective cell therapy for cardiac disease. We investigated the effects of intravenous delivery of BM-MSCs in the acute phase post-transplant in a heterotopic heart transplantation (HHT) model associated with I/R injury. Methods: Hearts of wild-type Lewis (WT LEW) rats were harvested and transplanted heterotopically into the necks of recipient WT LEW rats. Forty-eight hours after HHT, BM-MSCs were injected intravenously into animals in the experimental group, whereas controls received normal saline (NS). Results: Eight days after BM-MSC injection, fractional shortening of transplanted hearts was significantly higher and left ventricular systolic diameter was lower in the BM-MSC group compared with controls, whereas no differences were found 28 days after infusion. A reduction in ventricular remodeling and cardiac fibrosis was observed by histochemical analysis and confirmed by cardiac magnetic resonance imaging in the BM-MSC group. The perivascular stromal cells’ density and the number of capillaries were increased whereas the number of apoptotic cells decreased significantly in transplanted hearts in the BM-MSC group compared with the NS group. Conclusions: We showed early improvement in cardiac function and subsequent enhanced ventricular remodeling, reduced cardiac fibrosis, augmented neo-vascularization and decreased cardiomyocyte apoptosis of the transplanted heart in a heterotopic transplantation model after intravenous infusion of BM-derived MSCs. Our data suggest that clinical studies with BM-MSCs are warranted to understand their effects on cardiac graft and transplant recipient survival.
Fil: Montanari, Sonia. University Health Network; Canadá. University of Toronto; Canadá
Fil: Dayan, Victor. University Health Network; Canadá
Fil: Yannarelli, Gustavo Gabriel. University Health Network; Canadá. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Billia, Filio. Toronto General Hospital; Canadá
Fil: Viswanathan, Sowmya. University Health Network; Canadá
Fil: Connelly, Kim A.. Keenan Research Centre; Canadá
Fil: Keating, Armand. University Health Network; Canadá. University of Toronto; Canadá
description Background: Ischemia/reperfusion (I/R) injury is an inevitable consequence of organ transplantation and a major determinant of patient and graft survival in heart transplantation. Bone marrow–mesenchymal stromal cell (BM-MSC) treatment is a potentially effective cell therapy for cardiac disease. We investigated the effects of intravenous delivery of BM-MSCs in the acute phase post-transplant in a heterotopic heart transplantation (HHT) model associated with I/R injury. Methods: Hearts of wild-type Lewis (WT LEW) rats were harvested and transplanted heterotopically into the necks of recipient WT LEW rats. Forty-eight hours after HHT, BM-MSCs were injected intravenously into animals in the experimental group, whereas controls received normal saline (NS). Results: Eight days after BM-MSC injection, fractional shortening of transplanted hearts was significantly higher and left ventricular systolic diameter was lower in the BM-MSC group compared with controls, whereas no differences were found 28 days after infusion. A reduction in ventricular remodeling and cardiac fibrosis was observed by histochemical analysis and confirmed by cardiac magnetic resonance imaging in the BM-MSC group. The perivascular stromal cells’ density and the number of capillaries were increased whereas the number of apoptotic cells decreased significantly in transplanted hearts in the BM-MSC group compared with the NS group. Conclusions: We showed early improvement in cardiac function and subsequent enhanced ventricular remodeling, reduced cardiac fibrosis, augmented neo-vascularization and decreased cardiomyocyte apoptosis of the transplanted heart in a heterotopic transplantation model after intravenous infusion of BM-derived MSCs. Our data suggest that clinical studies with BM-MSCs are warranted to understand their effects on cardiac graft and transplant recipient survival.
publishDate 2015
dc.date.none.fl_str_mv 2015-11
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/11336/42282
Montanari, Sonia; Dayan, Victor; Yannarelli, Gustavo Gabriel; Billia, Filio; Viswanathan, Sowmya; et al.; Mesenchymal stromal cells improve cardiac function and left ventricular remodeling in a heart transplantation model; Elsevier Science Inc; Journal of Heart and Lung Transplantation; 34; 11; 11-2015; 1481-1488
1053-2498
CONICET Digital
CONICET
url http://hdl.handle.net/11336/42282
identifier_str_mv Montanari, Sonia; Dayan, Victor; Yannarelli, Gustavo Gabriel; Billia, Filio; Viswanathan, Sowmya; et al.; Mesenchymal stromal cells improve cardiac function and left ventricular remodeling in a heart transplantation model; Elsevier Science Inc; Journal of Heart and Lung Transplantation; 34; 11; 11-2015; 1481-1488
1053-2498
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.healun.2015.05.008
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S1053249815012796
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Science Inc
publisher.none.fl_str_mv Elsevier Science Inc
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_ 1842268816234512384
score 13.13397

Publicaciones similares