Development of cellularized and functionalized collagen scaffolds for the treatment of myocardial infarction

Cardiovascular diseases (CVD) are the leading cause of death in the developed countries. According to the las report of the European Society of Cardiology, CVD remain the most common cause of death within Europe, accounting for 2.2 million deaths in females and 1.9 million deaths in males. These equ...

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Detalhes bibliográficos
Autor: Pérez-Estenaga, I. (Iñigo)|||/items/0d3c0f0f-c86e-4bac-a8cb-20efdddb5d2d
Formato: tesis doctoral
Fecha de publicación:2020
País:España
Recursos:Universidad de Navarra
Repositorio:Dadun. Depósito Académico Digital de la Universidad de Navarra
Idioma:inglés
OAI Identifier:oai:dadun.unav.edu:10171/60694
Acesso em linha:https://hdl.handle.net/10171/60694
Access Level:acceso abierto
Palavra-chave:Materias Investigacion::Ciencias de la vida::Citología, biología celular
Materias Investigacion::Ciencias de la Salud::Microbiología y biología molecular
Materias Investigacion::Ciencias de la vida::Inmunología
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spelling Development of cellularized and functionalized collagen scaffolds for the treatment of myocardial infarctionPérez-Estenaga, I. (Iñigo)|||/items/0d3c0f0f-c86e-4bac-a8cb-20efdddb5d2dMaterias Investigacion::Ciencias de la vida::Citología, biología celularMaterias Investigacion::Ciencias de la Salud::Microbiología y biología molecularMaterias Investigacion::Ciencias de la vida::InmunologíaCardiovascular diseases (CVD) are the leading cause of death in the developed countries. According to the las report of the European Society of Cardiology, CVD remain the most common cause of death within Europe, accounting for 2.2 million deaths in females and 1.9 million deaths in males. These equate to 47% and 39% of all deaths in females and males, respectively, and almost half of them are caused by Myocardial Infarction (MI). In the last 20 years, in order to overcome the limitations of the conventional treatments, cell therapy, has emerged as a promising therapeutic option for the treatment of MI. In this thesis we have employed Adipose Derived Mesenchymal Stem Cells (ADSC) seeded in a collagen scaffold fabricated under GMP-conditions, to treat the infarcted heart in preclinical MI animal models. First, we assessed the patch safety in rodent models, proving a safe profile of the system, established by tumorigenicity, toxicity and biodistribution studies. Secondly, the collagen scaffold was cellularized with allogeneic ADSC and its immunological effect was analysed both in vitro and in vivo, showing no alloreactive response by the immune cells towards the allogeneic patch. Moreover in vitro, in a human context, the cellularized patch elicited a potent immunomodulatory effect towards lymphocytes by inhibiting their proliferation, phenotypical activation and pro-inflammatory cytokine production. Finally, the functionalization of the collagen membrane with the angiogenic factor SDF-1 was achieved, by the creation of a bilayer collagen scaffold, which confirmed to be biocompatible in vivo and exerted a therapeutic effect when tested in a rat MI model in the shape of cardiac function recovery.Universidad de NavarraPelacho-Samper, B. (Beatriz)Dadun. Depósito Académico Digital Universidad de Navarra20212021-06-1520212021-06-1520212021-06-1520202020-11-13doctoral thesishttp://purl.org/coar/resource_type/c_db06info:eu-repo/semantics/doctoralThesisapplication/pdfhttps://hdl.handle.net/10171/60694reponame:Dadun. Depósito Académico Digital de la Universidad de Navarrainstname:Universidad de NavarraInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:dadun.unav.edu:10171/606942026-06-21T12:47:57Z
dc.title.none.fl_str_mv Development of cellularized and functionalized collagen scaffolds for the treatment of myocardial infarction
title Development of cellularized and functionalized collagen scaffolds for the treatment of myocardial infarction
spellingShingle Development of cellularized and functionalized collagen scaffolds for the treatment of myocardial infarction
Pérez-Estenaga, I. (Iñigo)|||/items/0d3c0f0f-c86e-4bac-a8cb-20efdddb5d2d
Materias Investigacion::Ciencias de la vida::Citología, biología celular
Materias Investigacion::Ciencias de la Salud::Microbiología y biología molecular
Materias Investigacion::Ciencias de la vida::Inmunología
title_short Development of cellularized and functionalized collagen scaffolds for the treatment of myocardial infarction
title_full Development of cellularized and functionalized collagen scaffolds for the treatment of myocardial infarction
title_fullStr Development of cellularized and functionalized collagen scaffolds for the treatment of myocardial infarction
title_full_unstemmed Development of cellularized and functionalized collagen scaffolds for the treatment of myocardial infarction
title_sort Development of cellularized and functionalized collagen scaffolds for the treatment of myocardial infarction
dc.creator.none.fl_str_mv Pérez-Estenaga, I. (Iñigo)|||/items/0d3c0f0f-c86e-4bac-a8cb-20efdddb5d2d
author Pérez-Estenaga, I. (Iñigo)|||/items/0d3c0f0f-c86e-4bac-a8cb-20efdddb5d2d
author_facet Pérez-Estenaga, I. (Iñigo)|||/items/0d3c0f0f-c86e-4bac-a8cb-20efdddb5d2d
author_role author
dc.contributor.none.fl_str_mv Pelacho-Samper, B. (Beatriz)
Dadun. Depósito Académico Digital Universidad de Navarra
dc.subject.none.fl_str_mv Materias Investigacion::Ciencias de la vida::Citología, biología celular
Materias Investigacion::Ciencias de la Salud::Microbiología y biología molecular
Materias Investigacion::Ciencias de la vida::Inmunología
topic Materias Investigacion::Ciencias de la vida::Citología, biología celular
Materias Investigacion::Ciencias de la Salud::Microbiología y biología molecular
Materias Investigacion::Ciencias de la vida::Inmunología
description Cardiovascular diseases (CVD) are the leading cause of death in the developed countries. According to the las report of the European Society of Cardiology, CVD remain the most common cause of death within Europe, accounting for 2.2 million deaths in females and 1.9 million deaths in males. These equate to 47% and 39% of all deaths in females and males, respectively, and almost half of them are caused by Myocardial Infarction (MI). In the last 20 years, in order to overcome the limitations of the conventional treatments, cell therapy, has emerged as a promising therapeutic option for the treatment of MI. In this thesis we have employed Adipose Derived Mesenchymal Stem Cells (ADSC) seeded in a collagen scaffold fabricated under GMP-conditions, to treat the infarcted heart in preclinical MI animal models. First, we assessed the patch safety in rodent models, proving a safe profile of the system, established by tumorigenicity, toxicity and biodistribution studies. Secondly, the collagen scaffold was cellularized with allogeneic ADSC and its immunological effect was analysed both in vitro and in vivo, showing no alloreactive response by the immune cells towards the allogeneic patch. Moreover in vitro, in a human context, the cellularized patch elicited a potent immunomodulatory effect towards lymphocytes by inhibiting their proliferation, phenotypical activation and pro-inflammatory cytokine production. Finally, the functionalization of the collagen membrane with the angiogenic factor SDF-1 was achieved, by the creation of a bilayer collagen scaffold, which confirmed to be biocompatible in vivo and exerted a therapeutic effect when tested in a rat MI model in the shape of cardiac function recovery.
publishDate 2020
dc.date.none.fl_str_mv 2020
2020-11-13
2021
2021-06-15
2021
2021-06-15
2021
2021-06-15
dc.type.none.fl_str_mv doctoral thesis
http://purl.org/coar/resource_type/c_db06
dc.type.openaire.fl_str_mv info:eu-repo/semantics/doctoralThesis
format doctoralThesis
dc.identifier.none.fl_str_mv https://hdl.handle.net/10171/60694
url https://hdl.handle.net/10171/60694
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
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
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Universidad de Navarra
publisher.none.fl_str_mv Universidad de Navarra
dc.source.none.fl_str_mv reponame:Dadun. Depósito Académico Digital de la Universidad de Navarra
instname:Universidad de Navarra
instname_str Universidad de Navarra
reponame_str Dadun. Depósito Académico Digital de la Universidad de Navarra
collection Dadun. Depósito Académico Digital de la Universidad de Navarra
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,301603

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