Intrapericardial Delivery of APA-Microcapsules as Promising Stem Cell Therapy Carriers in an Experimental Acute Myocardial Infarction Model

The administration of cardiosphere-derived cells (CDCs) after acute myocardial infarction (AMI) is very promising. CDC encapsulation in alginate-poly-<span style="font-variant: small-caps;">l</span>-lysine-alginate (APA) could increase cell survival and adherence. The intraperi...

Full description

Bibliographic Details
Main Authors: Claudia Báez-Díaz, Virginia Blanco-Blázquez, Francisco Miguel Sánchez-Margallo, Esther López, Helena Martín, Albert Espona-Noguera, Javier G. Casado, Jesús Ciriza, José Luis Pedraz, Verónica Crisóstomo
Format: Article
Language:English
Published: MDPI AG 2021-11-01
Series:Pharmaceutics
Subjects:
Online Access:https://www.mdpi.com/1999-4923/13/11/1824
_version_ 1797508782528397312
author Claudia Báez-Díaz
Virginia Blanco-Blázquez
Francisco Miguel Sánchez-Margallo
Esther López
Helena Martín
Albert Espona-Noguera
Javier G. Casado
Jesús Ciriza
José Luis Pedraz
Verónica Crisóstomo
author_facet Claudia Báez-Díaz
Virginia Blanco-Blázquez
Francisco Miguel Sánchez-Margallo
Esther López
Helena Martín
Albert Espona-Noguera
Javier G. Casado
Jesús Ciriza
José Luis Pedraz
Verónica Crisóstomo
author_sort Claudia Báez-Díaz
collection DOAJ
description The administration of cardiosphere-derived cells (CDCs) after acute myocardial infarction (AMI) is very promising. CDC encapsulation in alginate-poly-<span style="font-variant: small-caps;">l</span>-lysine-alginate (APA) could increase cell survival and adherence. The intrapericardial (IP) approach potentially achieves high concentrations of the therapeutic agent in the infarcted area. We aimed to evaluate IP therapy using a saline vehicle as a control (CON), a dose of 30 × 10<sup>6</sup> CDCs (CDCs) or APA microcapsules containing 30 × 10<sup>6</sup> CDCs (APA-CDCs) at 72 h in a porcine AMI model. Magnetic resonance imaging (MRI) was used to determine the left ventricular ejection fraction (LVEF), infarct size (IS), and indexed end diastolic and systolic volumes (EDVi; ESVi) pre- and 10 weeks post-injection. Programmed electrical stimulation (PES) was performed to test arrhythmia inducibility before euthanasia. Histopathological analysis was carried out afterwards. The IP infusion was successful in all animals. At 10 weeks, MRI revealed significantly higher LVEF in the APA-CDC group compared with CON. No significant differences were observed among groups in IS, EDVi, ESVi, PES and histopathological analyses. In conclusion, the IP injection of CDCs (microencapsulated or not) was feasible and safe 72 h post-AMI in the porcine model. Moreover, CDCs APA encapsulation could have a beneficial effect on cardiac function, reflected by a higher LVEF at 10 weeks.
first_indexed 2024-03-10T05:08:47Z
format Article
id doaj.art-3e561752daf44aaa95fd92ae106f53c2
institution Directory Open Access Journal
issn 1999-4923
language English
last_indexed 2024-03-10T05:08:47Z
publishDate 2021-11-01
publisher MDPI AG
record_format Article
series Pharmaceutics
spelling doaj.art-3e561752daf44aaa95fd92ae106f53c22023-11-23T00:58:07ZengMDPI AGPharmaceutics1999-49232021-11-011311182410.3390/pharmaceutics13111824Intrapericardial Delivery of APA-Microcapsules as Promising Stem Cell Therapy Carriers in an Experimental Acute Myocardial Infarction ModelClaudia Báez-Díaz0Virginia Blanco-Blázquez1Francisco Miguel Sánchez-Margallo2Esther López3Helena Martín4Albert Espona-Noguera5Javier G. Casado6Jesús Ciriza7José Luis Pedraz8Verónica Crisóstomo9CIBERCV, Instituto de Salud Carlos III, 28029 Madrid, SpainCIBERCV, Instituto de Salud Carlos III, 28029 Madrid, SpainCIBERCV, Instituto de Salud Carlos III, 28029 Madrid, SpainFundación Centro de Cirugía de Mínima Invasión Jesús Usón, 10071 Cáceres, SpainFundación Centro de Cirugía de Mínima Invasión Jesús Usón, 10071 Cáceres, SpainCentro de Investigaciones y Estudios Avanzados Lucio Lascaray (CIEA), Laboratorio de Desarrollo y Evaluación de Medicamentos, 01006 Vitoria Gasteiz, SpainImmunology Unit-Institute of Molecular Pathology Biomarkers, Veterinary Faculty, University of Extremadura, 10003 Cáceres, SpainCIBER bbn, Instituto de Salud Carlos III, 28029 Madrid, SpainCentro de Investigaciones y Estudios Avanzados Lucio Lascaray (CIEA), Laboratorio de Desarrollo y Evaluación de Medicamentos, 01006 Vitoria Gasteiz, SpainCIBERCV, Instituto de Salud Carlos III, 28029 Madrid, SpainThe administration of cardiosphere-derived cells (CDCs) after acute myocardial infarction (AMI) is very promising. CDC encapsulation in alginate-poly-<span style="font-variant: small-caps;">l</span>-lysine-alginate (APA) could increase cell survival and adherence. The intrapericardial (IP) approach potentially achieves high concentrations of the therapeutic agent in the infarcted area. We aimed to evaluate IP therapy using a saline vehicle as a control (CON), a dose of 30 × 10<sup>6</sup> CDCs (CDCs) or APA microcapsules containing 30 × 10<sup>6</sup> CDCs (APA-CDCs) at 72 h in a porcine AMI model. Magnetic resonance imaging (MRI) was used to determine the left ventricular ejection fraction (LVEF), infarct size (IS), and indexed end diastolic and systolic volumes (EDVi; ESVi) pre- and 10 weeks post-injection. Programmed electrical stimulation (PES) was performed to test arrhythmia inducibility before euthanasia. Histopathological analysis was carried out afterwards. The IP infusion was successful in all animals. At 10 weeks, MRI revealed significantly higher LVEF in the APA-CDC group compared with CON. No significant differences were observed among groups in IS, EDVi, ESVi, PES and histopathological analyses. In conclusion, the IP injection of CDCs (microencapsulated or not) was feasible and safe 72 h post-AMI in the porcine model. Moreover, CDCs APA encapsulation could have a beneficial effect on cardiac function, reflected by a higher LVEF at 10 weeks.https://www.mdpi.com/1999-4923/13/11/1824CDCsAMIintrapericardialmicrocapsulesAPAswine
spellingShingle Claudia Báez-Díaz
Virginia Blanco-Blázquez
Francisco Miguel Sánchez-Margallo
Esther López
Helena Martín
Albert Espona-Noguera
Javier G. Casado
Jesús Ciriza
José Luis Pedraz
Verónica Crisóstomo
Intrapericardial Delivery of APA-Microcapsules as Promising Stem Cell Therapy Carriers in an Experimental Acute Myocardial Infarction Model
Pharmaceutics
CDCs
AMI
intrapericardial
microcapsules
APA
swine
title Intrapericardial Delivery of APA-Microcapsules as Promising Stem Cell Therapy Carriers in an Experimental Acute Myocardial Infarction Model
title_full Intrapericardial Delivery of APA-Microcapsules as Promising Stem Cell Therapy Carriers in an Experimental Acute Myocardial Infarction Model
title_fullStr Intrapericardial Delivery of APA-Microcapsules as Promising Stem Cell Therapy Carriers in an Experimental Acute Myocardial Infarction Model
title_full_unstemmed Intrapericardial Delivery of APA-Microcapsules as Promising Stem Cell Therapy Carriers in an Experimental Acute Myocardial Infarction Model
title_short Intrapericardial Delivery of APA-Microcapsules as Promising Stem Cell Therapy Carriers in an Experimental Acute Myocardial Infarction Model
title_sort intrapericardial delivery of apa microcapsules as promising stem cell therapy carriers in an experimental acute myocardial infarction model
topic CDCs
AMI
intrapericardial
microcapsules
APA
swine
url https://www.mdpi.com/1999-4923/13/11/1824
work_keys_str_mv AT claudiabaezdiaz intrapericardialdeliveryofapamicrocapsulesaspromisingstemcelltherapycarriersinanexperimentalacutemyocardialinfarctionmodel
AT virginiablancoblazquez intrapericardialdeliveryofapamicrocapsulesaspromisingstemcelltherapycarriersinanexperimentalacutemyocardialinfarctionmodel
AT franciscomiguelsanchezmargallo intrapericardialdeliveryofapamicrocapsulesaspromisingstemcelltherapycarriersinanexperimentalacutemyocardialinfarctionmodel
AT estherlopez intrapericardialdeliveryofapamicrocapsulesaspromisingstemcelltherapycarriersinanexperimentalacutemyocardialinfarctionmodel
AT helenamartin intrapericardialdeliveryofapamicrocapsulesaspromisingstemcelltherapycarriersinanexperimentalacutemyocardialinfarctionmodel
AT albertesponanoguera intrapericardialdeliveryofapamicrocapsulesaspromisingstemcelltherapycarriersinanexperimentalacutemyocardialinfarctionmodel
AT javiergcasado intrapericardialdeliveryofapamicrocapsulesaspromisingstemcelltherapycarriersinanexperimentalacutemyocardialinfarctionmodel
AT jesusciriza intrapericardialdeliveryofapamicrocapsulesaspromisingstemcelltherapycarriersinanexperimentalacutemyocardialinfarctionmodel
AT joseluispedraz intrapericardialdeliveryofapamicrocapsulesaspromisingstemcelltherapycarriersinanexperimentalacutemyocardialinfarctionmodel
AT veronicacrisostomo intrapericardialdeliveryofapamicrocapsulesaspromisingstemcelltherapycarriersinanexperimentalacutemyocardialinfarctionmodel