Abstract
Cardiac tissue engineering, which combines cells and supportive scaffolds, is an emerging treatment for restoring cardiac function after myocardial infarction (MI), although, the optimal construct remains a challenge. We developed two engineered cardiac grafts, based on decellularized scaffolds from myocardial and pericardial tissues and repopulated them with adipose tissue mesenchymal stem cells (ATMSCs). The structure, macromechanical and micromechanical scaffold properties were preserved upon the decellularization and recellularization processes, except for recellularized myocardium micromechanics that was ∼2-fold stiffer than native tissue and decellularized scaffolds. Proteome characterization of the two acellular matrices showed enrichment of matrisome proteins and major cardiac extracellular matrix components, considerably higher for the recellularized pericardium. Moreover, the pericardial scaffold demonstrated better cell penetrance and retention, as well as a bigger pore size. Both engineered cardiac grafts were further evaluated in pre-clinical MI swine models. Forty days after graft implantation, swine treated with the engineered cardiac grafts showed significant ventricular function recovery. Irrespective of the scaffold origin or cell recolonization, all scaffolds integrated with the underlying myocardium and showed signs of neovascularization and nerve sprouting. Collectively, engineered cardiac grafts -with pericardial or myocardial scaffolds- were effective in restoring cardiac function post-MI, and pericardial scaffolds showed better structural integrity and recolonization capability.
Highlights
Cardiac tissue engineering, which combines the use of cells and biomaterials, has been proposed as an alternative therapy for myocardial infarction (MI)[1], with the goals of repairing the damaged myocardium, recovering heart function, and preventing ventricular remodeling in end-stage heart failure
Seeding adipose tissue mesenchymal stem cells (ATMSCs) on top of the decellularized myocardium did not have a major impact on the matrix micromechanics; rather, it resulted in an overall preservation of the scaffold structure and mechanics following the recellularization process
We demonstrated that the implantation of the engineered cardiac grafts led to improvements in left ventricular ejection fraction (LVEF) and/or left ventricular end-systolic volume (LVESV), limited infarct size expansion, and coupling with the underlying myocardium, as indicated by the vascularization and innervation of the grafts
Summary
Cardiac tissue engineering, which combines the use of cells and biomaterials, has been proposed as an alternative therapy for myocardial infarction (MI)[1], with the goals of repairing the damaged myocardium, recovering heart function, and preventing ventricular remodeling in end-stage heart failure. Should closely resemble the physiological myocardial extracellular matrix (ECM) properties as internal scaffold conformation, mechanics, and composition will modulate cellular differentiation, migration, and adhesion[4,5,6,7,8]. In this context, decellularized cardiac tissues provide a close match to the native, physiological microenvironment, as they preserve the inherent stiffness, composition, vasculature network, and three-dimensional framework[9], and enable electromechanical coupling with the host myocardium upon implantation[10,11]. Cardiac function was analyzed with magnetic resonance imaging (MRI), and accurate infarct size was obtained with late gadolinium enhancement
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