title: Electromechanical Conditioning of Adult Progenitor Cells Improves Recovery of Cardiac Function After Myocardial Infarction.
abstract: Cardiac cells are subjected to mechanical and electrical forces, which regulate gene expression and cellular function. Therefore, in vitro electromechanical stimuli could benefit further integration of therapeutic cells into the myocardium. Our goals were (a) to study the viability of a tissue-engineered construct with cardiac adipose tissue-derived progenitor cells (cardiac ATDPCs) and (b) to examine the effect of electromechanically stimulated cardiac ATDPCs within a myocardial infarction (MI) model in mice for the first time. Cardiac ATDPCs were electromechanically stimulated at 2-millisecond pulses of 50 mV/cm at 1 Hz and 10% stretching during 7 days. The cells were harvested, labeled, embedded in a fibrin hydrogel, and implanted over the infarcted area of the murine heart. A total of 39 animals were randomly distributed and sacrificed at 21 days: groups of grafts without cells and with stimulated or nonstimulated cells. Echocardiography and gene and protein analyses were also carried out. Physiologically stimulated ATDPCs showed increased expression of cardiac transcription factors, structural genes, and calcium handling genes. At 21 days after implantation, cardiac function (measured as left ventricle ejection fraction between presacrifice and post-MI) increased up to 12% in stimulated grafts relative to nontreated animals. Vascularization and integration with the host blood supply of grafts with stimulated cells resulted in increased vessel density in the infarct border region. Trained cells within the implanted fibrin patch expressed main cardiac markers and migrated into the underlying ischemic myocardium. To conclude, synchronous electromechanical cell conditioning before delivery may be a preferred alternative when considering strategies for heart repair after myocardial infarction. Stem Cells Translational Medicine 2017;6:970-981.
authors.affiliation: Heart Failure and Cardiac Regeneration Research Programme, Health Science Research Institute Germans Trias i Pujol, Badalona, Spain.
authors.forename: Aida
authors.initials: A
authors.lastname: Llucià-Valldeperas
authors.affiliation: Heart Failure and Cardiac Regeneration Research Programme, Health Science Research Institute Germans Trias i Pujol, Badalona, Spain.
authors.forename: Carolina
authors.initials: C
authors.lastname: Soler-Botija
authors.affiliation: Heart Failure and Cardiac Regeneration Research Programme, Health Science Research Institute Germans Trias i Pujol, Badalona, Spain.
authors.forename: Carolina
authors.initials: C
authors.lastname: Gálvez-Montón
authors.affiliation: Heart Failure and Cardiac Regeneration Research Programme, Health Science Research Institute Germans Trias i Pujol, Badalona, Spain.|Center of Regenerative Medicine in Barcelona, Barcelona, Spain.
authors.forename: Santiago
authors.initials: S
authors.lastname: Roura
authors.affiliation: Heart Failure and Cardiac Regeneration Research Programme, Health Science Research Institute Germans Trias i Pujol, Badalona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Prat-Vidal
authors.affiliation: Heart Failure and Cardiac Regeneration Research Programme, Health Science Research Institute Germans Trias i Pujol, Badalona, Spain.
authors.forename: Isaac
authors.initials: I
authors.lastname: Perea-Gil
authors.affiliation: Electronic and Biomedical Instrumentation Group, Departament d'Enginyeria Electrònica, Universitat Politècnica de Catalunya, Barcelona, Spain.|Department of Neurology, Division of Neuromuscular Diseases, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Sanchez
authors.affiliation: Electronic and Biomedical Instrumentation Group, Departament d'Enginyeria Electrònica, Universitat Politècnica de Catalunya, Barcelona, Spain.
authors.forename: Ramon
authors.initials: R
authors.lastname: Bragos
authors.affiliation: Department of Biomedical Engineering, Columbia University, New York, New York, USA.|Department of Medicine, Columbia University, New York, New York, USA.
authors.forename: Gordana
authors.initials: G
authors.lastname: Vunjak-Novakovic
authors.affiliation: Heart Failure and Cardiac Regeneration Research Programme, Health Science Research Institute Germans Trias i Pujol, Badalona, Spain.|Cardiology Service, Hospital Universitari Germans Trias i Pujol, Badalona, Spain.|Department of Medicine, Universitat Autònoma de Barcelona, Bellaterra, Spain.
authors.forename: Antoni
authors.initials: A
authors.lastname: Bayes-Genis
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology / Q000187:drug effects / Q000637:transplantation*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005337:Fibrin / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006334:Heart Function Tests; D006801:Humans; D016513:Mice, SCID; D009203:Myocardial Infarction / Q000503:physiopathology* / Q000628:therapy*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000187:drug effects; D019919:Prosthesis Implantation; D020127:Recovery of Function / Q000187:drug effects; D033581:Stem Cell Transplantation; D023822:Tissue Engineering; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D005337:Fibrin
keywords: Biophysical stimulation; Cardiac adipose tissue-derived progenitor cells; Cardiac regeneration; Electromechanical conditioning; Myocardial infarction; Tissue engineering