Abstract

The epicardial administration of therapeutics via the pericardial sac offers an attractive route, since it is minimally invasive and carries no risks of coronary embolization. The aim of this study was to assess viability, safety and effectiveness of cardiosphere-derived cells (CDCs), their extracellular vesicles (EVs) or placebo administered via a mini-thoracotomy 72 h after experimental infarction in swine. The epicardial administration was completed successfully in all cases in a surgery time (knife-to-skin) below 30 min. No significant differences between groups were found in cardiac function parameters evaluated using magnetic resonance imaging before therapy and at the end of the study, despite a trend towards improved function in CDC-treated animals. Moreover, infarct size at 10 weeks was smaller in treated animals, albeit not significantly. Arrhythmia inducibility did not differ between groups. Pathological examination showed no differences, nor were there any pericardial adhesions evidenced in any case 10 weeks after surgery. These results show that the epicardial delivery of CDCs or their EVs is safe and technically easy 3 days after experimental myocardial infarction in swine, but it does not appear to have any beneficial effect on cardiac function. Our results do not support clinical translation of these therapies as implemented in this work.

Details

Title
The epicardial delivery of cardiosphere derived cells or their extracellular vesicles is safe but of limited value in experimental infarction
Author
Crisóstomo Verónica 1 ; Baéz-Diaz, Claudia 1 ; Blanco-Blázquez, Virginia 1 ; Álvarez Verónica 2 ; López-Nieto, Esther 2 ; Maestre, Juan 1 ; Bayes-Genis Antoni 3 ; Gálvez-Montón Carolina 3 ; Casado, Javier G 4 ; Sánchez-Margallo, Francisco M 1 

 Fundación Centro de Cirugía de Mínima Invasión Jesús Usón, Cáceres, Spain (GRID:grid.419856.7) (ISNI:0000 0001 1849 4430); Instituto de Salud Carlos III, CIBERCV, Madrid, Spain (GRID:grid.413448.e) (ISNI:0000 0000 9314 1427) 
 Fundación Centro de Cirugía de Mínima Invasión Jesús Usón, Cáceres, Spain (GRID:grid.419856.7) (ISNI:0000 0001 1849 4430) 
 Instituto de Salud Carlos III, CIBERCV, Madrid, Spain (GRID:grid.413448.e) (ISNI:0000 0000 9314 1427); Institut d’Investigació en Ciències de la Salut Germans Trias i Pujol, ICREC Research Group (Insuficiència Cardíaca i REgeneració Cardíaca), Badalona, Spain (GRID:grid.429186.0) 
 Fundación Centro de Cirugía de Mínima Invasión Jesús Usón, Cáceres, Spain (GRID:grid.419856.7) (ISNI:0000 0001 1849 4430); Instituto de Salud Carlos III, CIBERCV, Madrid, Spain (GRID:grid.413448.e) (ISNI:0000 0000 9314 1427); University of Extremadura, Immunology Unit, Cáceres, Spain (GRID:grid.8393.1) (ISNI:0000000119412521); University of Extremadura, Institute of Molecular Pathology Biomarkers, Cáceres, Spain (GRID:grid.8393.1) (ISNI:0000000119412521) 
Publication year
2021
Publication date
2021
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2596809142
Copyright
© The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.