Abstract
Cardiac patch is considered a promising strategy for enhancing stem cell therapy of myocardial infarction (MI). However, the underlying mechanisms for cardiac patch repairing infarcted myocardium remain unclear. In this study, we investigated the mechanisms of PCL/gelatin patch loaded with MSCs on activating endogenous cardiac repair. PCL/gelatin patch was fabricated by electrospun. The patch enhanced the survival of the seeded MSCs and their HIF‐1α, Tβ4, VEGF and SDF‐1 expression and decreased CXCL14 expression in hypoxic and serum‐deprived conditions. In murine MI models, the survival and distribution of the engrafted MSCs and the activation of the epicardium were examined, respectively. At 4 weeks after transplantation of the cell patch, the cardiac functions were significantly improved. The engrafted MSCs migrated across the epicardium and into the myocardium. Tendency of HIF‐1α, Tβ4, VEGF, SDF‐1 and CXCL14 expression in the infarcted myocardium was similar with expression in vitro. The epicardium was activated and epicardial‐derived cells (EPDCs) migrated into deep tissue. The EPDCs differentiated into endothelial cells and smooth muscle cells, and some of EPDCs showed to have differentiated into cardiomyocytes. Density of blood and lymphatic capillaries increased significantly. More c‐kit+ cells were recruited into the infarcted myocardium after transplantation of the cell patch. The results suggest that epicardial transplantation of the cell patch promotes repair of the infarcted myocardium and improves cardiac functions by enhancing the survival of the transplanted cells, accelerating locality paracrine, and then activating the epicardium and recruiting endogenous c‐kit+ cells. Epicardial transplantation of the cell patch may be applied as a novel effective MI therapy.
Highlights
myocardial infarction (MI) is a leading cause of death of the cardiovascular diseases in the developed and developing countries
The present study demonstrates that epicardial transplantation of mesenchymal stem cells (MSCs)-loaded PCL/gelatin patch is an effective therapeutic strategy for repairing the infarcted myocardium and improving cardiac function
Both the transplanted cells and epicardial-derived cells (EPDCs) activated by the cell patch contribute to repair of the infracted myocardium
Summary
MI is a leading cause of death of the cardiovascular diseases in the developed and developing countries. The overall prevalence for MI is 2.8% in US adults. MI prevalence is 4.0% for men and 1.8% for women [1]. According to investigation of the European Society of Cardiology, one in six men and one in seven women in Europe will die from MI [2]. The patients die of heart failure or arrhythmia . Percutaneous coronary intervention and pharmacotherapy using diuretics, angiotensin-converting enzyme inhibitors and b-adrenergic receptor antagonists have significantly reduced MI mortality. These therapies may improve cardiac functions to some degree; the lost cardiomyocytes cannot be regained. Heart transplantation is often required at end-stage heart failure, this therapy is limited by the shortage of organ donors and long-term immune rejection
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