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

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. We performed a blind, randomized, placebo-controlled APC therapy trial in a swine model of re...

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Autores: Alvino, Valeria Vicenza, Fernández-Jiménez, Rodrigo, Rodriguez-Arabaolaza, Iker, Slater, Sadie, Mangialardi, Giuseppe, Avolio, Elisa, Spencer, Helen, Culliford, Lucy, Hassan, Sakinah, Sueiro Ballesteros, Lorena, Herman, Andrew, Ayaon-Albarrán, Ali, Galán-Arriola, Carlos, Sánchez-González, Javier, Hennessey, Helena, Delmege, Catherine, Ascione, Raimondo, Emanueli, Costanza, Angelini, Gianni Davide, Ibanez, Borja, Madeddu, Paolo
Tipo de recurso: artículo
Fecha de publicación:2018
País:España
Institución:Universidad Camilo José Cela (UCJC)
Repositorio:Depósito Digital e-UCJC
OAI Identifier:oai:repositorio.ucjc.edu:20.500.12020/1584
Acceso en línea:http://hdl.handle.net/20.500.12020/1584
https://doi.org/10.1161/jaha.117.006727
Access Level:acceso abierto
Palabra clave:Biología Celular y Molecular
Angiogenesis
Cell Therapy
Large Animal Models
Myocardial Infarction
Pericytes
32 Ciencias Médicas
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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 VicenzaFernández-Jiménez, RodrigoRodriguez-Arabaolaza, IkerSlater, SadieMangialardi, GiuseppeAvolio, ElisaSpencer, HelenCulliford, LucyHassan, SakinahSueiro Ballesteros, LorenaHerman, AndrewAyaon-Albarrán, AliGalán-Arriola, CarlosSánchez-González, JavierHennessey, HelenaDelmege, CatherineAscione, RaimondoEmanueli, CostanzaAngelini, Gianni DavideIbanez, BorjaMadeddu, PaoloBiología Celular y MolecularAngiogenesisCell TherapyLarge Animal ModelsMyocardial InfarctionPericytes32 Ciencias MédicasTransplantation 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. 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 in vitro 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. 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.2018info:eu-repo/semantics/articlehttp://hdl.handle.net/20.500.12020/1584https://doi.org/10.1161/jaha.117.006727reponame:Depósito Digital e-UCJCinstname:Universidad Camilo José Cela (UCJC)Inglésinfo:eu-repo/semantics/openAccessoai:repositorio.ucjc.edu:20.500.12020/15842026-05-27T07:36:51Z
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 Vicenza
Biología Celular y Molecular
Angiogenesis
Cell Therapy
Large Animal Models
Myocardial Infarction
Pericytes
32 Ciencias Médicas
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 Vicenza
Fernández-Jiménez, Rodrigo
Rodriguez-Arabaolaza, Iker
Slater, Sadie
Mangialardi, Giuseppe
Avolio, Elisa
Spencer, Helen
Culliford, Lucy
Hassan, Sakinah
Sueiro Ballesteros, Lorena
Herman, Andrew
Ayaon-Albarrán, Ali
Galán-Arriola, Carlos
Sánchez-González, Javier
Hennessey, Helena
Delmege, Catherine
Ascione, Raimondo
Emanueli, Costanza
Angelini, Gianni Davide
Ibanez, Borja
Madeddu, Paolo
author Alvino, Valeria Vicenza
author_facet Alvino, Valeria Vicenza
Fernández-Jiménez, Rodrigo
Rodriguez-Arabaolaza, Iker
Slater, Sadie
Mangialardi, Giuseppe
Avolio, Elisa
Spencer, Helen
Culliford, Lucy
Hassan, Sakinah
Sueiro Ballesteros, Lorena
Herman, Andrew
Ayaon-Albarrán, Ali
Galán-Arriola, Carlos
Sánchez-González, Javier
Hennessey, Helena
Delmege, Catherine
Ascione, Raimondo
Emanueli, Costanza
Angelini, Gianni Davide
Ibanez, Borja
Madeddu, Paolo
author_role author
author2 Fernández-Jiménez, Rodrigo
Rodriguez-Arabaolaza, Iker
Slater, Sadie
Mangialardi, Giuseppe
Avolio, Elisa
Spencer, Helen
Culliford, Lucy
Hassan, Sakinah
Sueiro Ballesteros, Lorena
Herman, Andrew
Ayaon-Albarrán, Ali
Galán-Arriola, Carlos
Sánchez-González, Javier
Hennessey, Helena
Delmege, Catherine
Ascione, Raimondo
Emanueli, Costanza
Angelini, Gianni Davide
Ibanez, 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.subject.none.fl_str_mv Biología Celular y Molecular
Angiogenesis
Cell Therapy
Large Animal Models
Myocardial Infarction
Pericytes
32 Ciencias Médicas
topic Biología Celular y Molecular
Angiogenesis
Cell Therapy
Large Animal Models
Myocardial Infarction
Pericytes
32 Ciencias Médicas
description 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. 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 in vitro 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. 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
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12020/1584
https://doi.org/10.1161/jaha.117.006727
url http://hdl.handle.net/20.500.12020/1584
https://doi.org/10.1161/jaha.117.006727
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv reponame:Depósito Digital e-UCJC
instname:Universidad Camilo José Cela (UCJC)
instname_str Universidad Camilo José Cela (UCJC)
reponame_str Depósito Digital e-UCJC
collection Depósito Digital e-UCJC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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