title: Noninvasive Assessment of an Engineered Bioactive Graft in Myocardial Infarction: Impact on Cardiac Function and Scar Healing.
abstract: Cardiac tissue engineering, which combines cells and biomaterials, is promising for limiting the sequelae of myocardial infarction (MI). We assessed myocardial function and scar evolution after implanting an engineered bioactive impedance graft (EBIG) in a swine MI model. The EBIG comprises a scaffold of decellularized human pericardium, green fluorescent protein-labeled porcine adipose tissue-derived progenitor cells (pATPCs), and a customized-design electrical impedance spectroscopy (EIS) monitoring system. Cardiac function was evaluated noninvasively by using magnetic resonance imaging (MRI). Scar healing was evaluated by using the EIS system within the implanted graft. Additionally, infarct size, fibrosis, and inflammation were explored by histopathology. Upon sacrifice 1 month after the intervention, MRI detected a significant improvement in left ventricular ejection fraction (7.5% ± 4.9% vs. 1.4% ± 3.7%; p = .038) and stroke volume (11.5 ± 5.9 ml vs. 3 ± 4.5 ml; p = .019) in EBIG-treated animals. Noninvasive EIS data analysis showed differences in both impedance magnitude ratio (-0.02 ± 0.04 per day vs. -0.48 ± 0.07 per day; p = .002) and phase angle slope (-0.18° ± 0.24° per day vs. -3.52° ± 0.84° per day; p = .004) in EBIG compared with control animals. Moreover, in EBIG-treated animals, the infarct size was 48% smaller (3.4% ± 0.6% vs. 6.5% ± 1%; p = .015), less inflammation was found by means of CD25+lymphocytes (0.65 ± 0.12 vs. 1.26 ± 0.2; p = .006), and a lower collagen I/III ratio was detected (0.49 ± 0.06 vs. 1.66 ± 0.5; p = .019). An EBIG composed of acellular pericardium refilled with pATPCs significantly reduced infarct size and improved cardiac function in a preclinical model of MI. Noninvasive EIS monitoring was useful for tracking differential scar healing in EBIG-treated animals, which was confirmed by less inflammation and altered collagen deposit. Stem Cells Translational Medicine 2017;6:647-655.
authors.affiliation: ICREC (Heart Failure and Cardiac Regeneration) Research Programme, Fundació Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Badalona, Barcelona, Spain.
authors.forename: Carolina
authors.initials: C
authors.lastname: Gálvez-Montón
authors.affiliation: Electronic and Biomedical Instrumentation Group, Electronic Engineering Department, Universitat Politècnica de Catalunya, Barcelona, Spain.
authors.forename: Ramon
authors.initials: R
authors.lastname: Bragós
authors.affiliation: ICREC (Heart Failure and Cardiac Regeneration) Research Programme, Fundació Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Badalona, Barcelona, Spain.
authors.forename: Carolina
authors.initials: C
authors.lastname: Soler-Botija
authors.affiliation: Jesús Usón Minimally Invasive Surgery Centre, Cáceres, Spain.
authors.forename: Idoia
authors.initials: I
authors.lastname: Díaz-Güemes
authors.affiliation: ICREC (Heart Failure and Cardiac Regeneration) Research Programme, Fundació Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Badalona, Barcelona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Prat-Vidal
authors.affiliation: Jesús Usón Minimally Invasive Surgery Centre, Cáceres, Spain.
authors.forename: Verónica
authors.initials: V
authors.lastname: Crisóstomo
authors.affiliation: Jesús Usón Minimally Invasive Surgery Centre, Cáceres, Spain.
authors.forename: Francisco M
authors.initials: FM
authors.lastname: Sánchez-Margallo
authors.affiliation: ICREC (Heart Failure and Cardiac Regeneration) Research Programme, Fundació Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Badalona, Barcelona, Spain.
authors.forename: Aida
authors.initials: A
authors.lastname: Llucià-Valldeperas
authors.affiliation: Electronic and Biomedical Instrumentation Group, Electronic Engineering Department, Universitat Politècnica de Catalunya, Barcelona, Spain.
authors.forename: Paco
authors.initials: P
authors.lastname: Bogónez-Franco
authors.affiliation: ICREC (Heart Failure and Cardiac Regeneration) Research Programme, Fundació Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Badalona, Barcelona, Spain.
authors.forename: Isaac
authors.initials: I
authors.lastname: Perea-Gil
authors.affiliation: ICREC (Heart Failure and Cardiac Regeneration) Research Programme, Fundació Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Badalona, Barcelona, Spain.|Center of Regenerative Medicine in Barcelona, Barcelona, Spain.
authors.forename: Santiago
authors.initials: S
authors.lastname: Roura
authors.affiliation: ICREC (Heart Failure and Cardiac Regeneration) Research Programme, Fundació Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Badalona, Barcelona, Spain.|Cardiology Service, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain.|Department of Medicine, Autonomous University of Barcelona, Barcelona, Spain.
authors.forename: Antoni
authors.initials: A
authors.lastname: Bayes-Genis
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D058266:Dielectric Spectroscopy; D004195:Disease Models, Animal; D006801:Humans; D008279:Magnetic Resonance Imaging; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D010641:Phenotype; D020127:Recovery of Function; D012038:Regeneration; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000378:metabolism; D013318:Stroke Volume; D034421:Sus scrofa; D013997:Time Factors; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling
keywords: Angiogenesis; Bioimpedance; Magnetic resonance imaging; Myocardial infarction; Progenitor cells