Adipose Stem Cell-Seeded Decellularized Porcine Pericardium: A Promising Functional Biomaterial to Synergistically Restore the Cardiac Functions Post-Myocardial Infarction

SIMPLE SUMMARY: Over the years, diverse therapeutic protocols have been employed for cardiac tissue engineering (CTE) and improvement of the heart functions. Among them are stem cells which possess a high tissue-regeneration potential. However, the optimum delivery protocol with effective cell retention and homing at the target site is still challenging. Hence, a wide range of natural and synthetic biomaterials have been utilized as cell delivery cargoes to address these limitations. Natural decellularized biomaterials could provide successful biocompatible, biodegradable, elastic, and strong platforms that avoid the drawbacks of synthetic ones. Hence, in the present study, we have prepared a decellularized porcine pericardium (DPP) patch to provide successful tailored cell discharge, retention, and homing at the site of the myocardial infarction (MI) with an outstanding ability to restore the damaged heart activity. Moreover, we have provided for the first time a novel echocardiographic-derived imaging modality called the intraventricular pressure gradient (IVPG) to evaluate the process. The IVPG provides a precise, non-invasive, and facile tool to assess cardiac functions. This speeds up the accumulation of knowledge and opens new avenues to objectively evaluate diagnosis and treatment, which encourages the implementation of such a cutting-edge strategy in clinical practices in the near future. ABSTRACT: Myocardial infarction (MI) is a serious cardiovascular disease as the leading cause of death globally. Hence, reconstruction of the cardiac tissue comes at the forefront of strategies adopted to restore heart functions following MI. In this investigation, we studied the capacity of rat adipose-derived mesenchymal stem cells (r-AdMSCs) and decellularized porcine pericardium (DPP) to restore heart functions in MI animals. MI was induced in four different groups, three of which were treated either using DPP (MI-DPP group), stem cells (MI-SC group), or both (MI-SC/DPP group). Cardiac functions of these groups and the Sham group were evaluated using echocardiography, the intraventricular pressure gradient (IVPG) on weeks 2 and 4, and intraventricular hemodynamics on week 4. On day 31, the animals were euthanized for histological analysis. Echocardiographic, IVPG and hemodynamic findings indicated that the three treatment strategies shared effectively in the regeneration process. However, the MI-SC/DPP group had a unique synergistic ability to restore heart functions superior to the other treatment protocols. Histology showed that the MI-SC/DPP group presented the lowest (p < 0.05) degeneration score and fibrosis % compared to the other groups. Conclusively, stem cell-seeded DPP is a promising platform for the delivery of stem cells and restoration of heart functions post-MI.