Transplantation of Allogeneic Pericytes Improves Myocardial Vascularization and Reduces Interstitial Fibrosis in a Swine Model of Reperfused Acute Myocardial Infarction

Background-Transplantation of adventitial pericytes (APCs) promotes cardiac repair in murine models of myocardial infarction. The aim of present study was to confirm the benefit of APC therapy in a large animal model. Methods and Results-We performed a blind, randomized, placebo-controlled APC thera...

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Autores: Alvino, Valeria Vincenza, Fernandez-Jimenez, Rodrigo, Rodriguez-Arabaolaza, Iker, Slater, Sadie, Mangialardi, Giuseppe, Avolio, Elisa, Spencer, Helen, Culliford, Lucy, Hassan, Sakinah, Sueiro Ballesteros, Lorena, Herman, Andrew, Ayaon-Albarran, Ali, Galan-Arriola, Carlos, Sanchez-Gonzalez, Javier, Hennessey, Helena, Delmege, Catherine, Ascione, Raimondo, Emanueli, Costanza, Angelini, Gianni, Ibáñez, Borja, Madeddu, Paolo
Formato: artículo
Fecha de publicación:2018
País:España
Recursos:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/6694
Acesso em linha:http://hdl.handle.net/20.500.12105/6694
Access Level:acceso abierto
Palavra-chave:Angiogenesis
Cell therapy
Large animal models
Myocardial infarction
Pericytes
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spelling Transplantation of Allogeneic Pericytes Improves Myocardial Vascularization and Reduces Interstitial Fibrosis in a Swine Model of Reperfused Acute Myocardial InfarctionAlvino, Valeria VincenzaFernandez-Jimenez, RodrigoRodriguez-Arabaolaza, IkerSlater, SadieMangialardi, GiuseppeAvolio, ElisaSpencer, HelenCulliford, LucyHassan, SakinahSueiro Ballesteros, LorenaHerman, AndrewAyaon-Albarran, AliGalan-Arriola, CarlosSanchez-Gonzalez, JavierHennessey, HelenaDelmege, CatherineAscione, RaimondoEmanueli, CostanzaAngelini, GianniIbáñez, BorjaMadeddu, PaoloAngiogenesisCell therapyLarge animal modelsMyocardial infarctionPericytesBackground-Transplantation of adventitial pericytes (APCs) promotes cardiac repair in murine models of myocardial infarction. The aim of present study was to confirm the benefit of APC therapy in a large animal model. Methods and Results-We performed a blind, randomized, placebo-controlled APC therapy trial in a swine model of reperfused myocardial infarction. A first study used human APCs (hAPCs) from patients undergoing coronary artery bypass graft surgery. A second study used allogeneic swine APCs (sAPCs). Primary end points were (1) ejection fraction as assessed by cardiac magnetic resonance imaging and (2) myocardial vascularization and fibrosis as determined by immunohistochemistry. Transplantation of hAPCs reduced fibrosis but failed to improve the other efficacy end points. Incompatibility of the xenogeneic model was suggested by the occurrence of a cytotoxic response following invitro challenge of hAPCs with swine spleen lymphocytes and the failure to retrieve hAPCs in transplanted hearts. We next considered sAPCs as an alternative. Flow cytometry, immunocytochemistry, and functional/cytotoxic assays indicate that sAPCs are a surrogate of hAPCs. Transplantation of allogeneic sAPCs benefited capillary density and fibrosis but did not improve cardiac magnetic resonance imaging indices of contractility. Transplanted cells were detected in the border zone. Conclusions-Immunologic barriers limit the applicability of a xenogeneic swine model to assess hAPC efficacy. On the other hand, we newly show that transplantation of allogeneic sAPCs is feasible, safe, and immunologically acceptable. The approach induces proangiogenic and antifibrotic benefits, though these effects were not enough to result in functional improvements.WileyBritish Heart FoundationMedical Research Council (Reino Unido)National Health Service (Reino Unido)Ministerio de Economía, Industria y Competitividad (España)Fundación Jesús SerraFundación Interhospitalaria de Investigación CardiovascularCentro Nacional de Investigaciones Cardiovasculares Carlos III (España)Instituto de Salud Carlos IIIFundación ProCNIC20182018-11-2220182018-01-0120182018-01-01journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfapplication/pdfhttp://hdl.handle.net/20.500.12105/6694reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)InglésengES SEV-2015-0505 Not availableopen accesshttp://purl.org/coar/access_right/c_abf2Atribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/66942026-06-12T12:43:37Z
dc.title.none.fl_str_mv Transplantation of Allogeneic Pericytes Improves Myocardial Vascularization and Reduces Interstitial Fibrosis in a Swine Model of Reperfused Acute Myocardial Infarction
title Transplantation of Allogeneic Pericytes Improves Myocardial Vascularization and Reduces Interstitial Fibrosis in a Swine Model of Reperfused Acute Myocardial Infarction
spellingShingle Transplantation of Allogeneic Pericytes Improves Myocardial Vascularization and Reduces Interstitial Fibrosis in a Swine Model of Reperfused Acute Myocardial Infarction
Alvino, Valeria Vincenza
Angiogenesis
Cell therapy
Large animal models
Myocardial infarction
Pericytes
title_short Transplantation of Allogeneic Pericytes Improves Myocardial Vascularization and Reduces Interstitial Fibrosis in a Swine Model of Reperfused Acute Myocardial Infarction
title_full Transplantation of Allogeneic Pericytes Improves Myocardial Vascularization and Reduces Interstitial Fibrosis in a Swine Model of Reperfused Acute Myocardial Infarction
title_fullStr Transplantation of Allogeneic Pericytes Improves Myocardial Vascularization and Reduces Interstitial Fibrosis in a Swine Model of Reperfused Acute Myocardial Infarction
title_full_unstemmed Transplantation of Allogeneic Pericytes Improves Myocardial Vascularization and Reduces Interstitial Fibrosis in a Swine Model of Reperfused Acute Myocardial Infarction
title_sort Transplantation of Allogeneic Pericytes Improves Myocardial Vascularization and Reduces Interstitial Fibrosis in a Swine Model of Reperfused Acute Myocardial Infarction
dc.creator.none.fl_str_mv Alvino, Valeria Vincenza
Fernandez-Jimenez, Rodrigo
Rodriguez-Arabaolaza, Iker
Slater, Sadie
Mangialardi, Giuseppe
Avolio, Elisa
Spencer, Helen
Culliford, Lucy
Hassan, Sakinah
Sueiro Ballesteros, Lorena
Herman, Andrew
Ayaon-Albarran, Ali
Galan-Arriola, Carlos
Sanchez-Gonzalez, Javier
Hennessey, Helena
Delmege, Catherine
Ascione, Raimondo
Emanueli, Costanza
Angelini, Gianni
Ibáñez, Borja
Madeddu, Paolo
author Alvino, Valeria Vincenza
author_facet Alvino, Valeria Vincenza
Fernandez-Jimenez, Rodrigo
Rodriguez-Arabaolaza, Iker
Slater, Sadie
Mangialardi, Giuseppe
Avolio, Elisa
Spencer, Helen
Culliford, Lucy
Hassan, Sakinah
Sueiro Ballesteros, Lorena
Herman, Andrew
Ayaon-Albarran, Ali
Galan-Arriola, Carlos
Sanchez-Gonzalez, Javier
Hennessey, Helena
Delmege, Catherine
Ascione, Raimondo
Emanueli, Costanza
Angelini, Gianni
Ibáñez, Borja
Madeddu, Paolo
author_role author
author2 Fernandez-Jimenez, Rodrigo
Rodriguez-Arabaolaza, Iker
Slater, Sadie
Mangialardi, Giuseppe
Avolio, Elisa
Spencer, Helen
Culliford, Lucy
Hassan, Sakinah
Sueiro Ballesteros, Lorena
Herman, Andrew
Ayaon-Albarran, Ali
Galan-Arriola, Carlos
Sanchez-Gonzalez, Javier
Hennessey, Helena
Delmege, Catherine
Ascione, Raimondo
Emanueli, Costanza
Angelini, Gianni
Ibáñez, Borja
Madeddu, Paolo
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv British Heart Foundation
Medical Research Council (Reino Unido)
National Health Service (Reino Unido)
Ministerio de Economía, Industria y Competitividad (España)
Fundación Jesús Serra
Fundación Interhospitalaria de Investigación Cardiovascular
Centro Nacional de Investigaciones Cardiovasculares Carlos III (España)
Instituto de Salud Carlos III
Fundación ProCNIC
dc.subject.none.fl_str_mv Angiogenesis
Cell therapy
Large animal models
Myocardial infarction
Pericytes
topic Angiogenesis
Cell therapy
Large animal models
Myocardial infarction
Pericytes
description Background-Transplantation of adventitial pericytes (APCs) promotes cardiac repair in murine models of myocardial infarction. The aim of present study was to confirm the benefit of APC therapy in a large animal model. Methods and Results-We performed a blind, randomized, placebo-controlled APC therapy trial in a swine model of reperfused myocardial infarction. A first study used human APCs (hAPCs) from patients undergoing coronary artery bypass graft surgery. A second study used allogeneic swine APCs (sAPCs). Primary end points were (1) ejection fraction as assessed by cardiac magnetic resonance imaging and (2) myocardial vascularization and fibrosis as determined by immunohistochemistry. Transplantation of hAPCs reduced fibrosis but failed to improve the other efficacy end points. Incompatibility of the xenogeneic model was suggested by the occurrence of a cytotoxic response following invitro challenge of hAPCs with swine spleen lymphocytes and the failure to retrieve hAPCs in transplanted hearts. We next considered sAPCs as an alternative. Flow cytometry, immunocytochemistry, and functional/cytotoxic assays indicate that sAPCs are a surrogate of hAPCs. Transplantation of allogeneic sAPCs benefited capillary density and fibrosis but did not improve cardiac magnetic resonance imaging indices of contractility. Transplanted cells were detected in the border zone. Conclusions-Immunologic barriers limit the applicability of a xenogeneic swine model to assess hAPC efficacy. On the other hand, we newly show that transplantation of allogeneic sAPCs is feasible, safe, and immunologically acceptable. The approach induces proangiogenic and antifibrotic benefits, though these effects were not enough to result in functional improvements.
publishDate 2018
dc.date.none.fl_str_mv 2018
2018-11-22
2018
2018-01-01
2018
2018-01-01
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12105/6694
url http://hdl.handle.net/20.500.12105/6694
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv ES SEV-2015-0505 Not available
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
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