Postinfarction Functional Recovery Driven by a Three-Dimensional Engineered Fibrin Patch Composed of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells

Abstract

Abstract Considerable research has been dedicated to restoring myocardial cell slippage and limiting ventricular remodeling after myocardial infarction (MI). We examined the ability of a three-dimensional (3D) engineered fibrin patch filled with human umbilical cord blood-derived mesenchymal stem cells (UCBMSCs) to induce recovery of cardiac function after MI. The UCBMSCs were modified to coexpress luciferase and fluorescent protein reporters, mixed with fibrin, and applied as an adhesive, viable construct (fibrin-cell patch) over the infarcted myocardium in mice (MI-UCBMSC group). The patch adhered well to the heart. Noninvasive bioluminescence imaging demonstrated early proliferation and differentiation of UCBMSCs within the construct in the postinfarct mice in the MI-UCBMSC group. The implanted cells also participated in the formation of new, functional microvasculature that connected the fibrin-cell patch to both the subjacent myocardial tissue and the host circulatory system. As revealed by echocardiography, the left ventricular ejection fraction and fractional shortening at sacrifice were improved in MI-UCBMSC mice and were markedly reduced in mice treated with fibrin alone and untreated postinfarction controls. In conclusion, a 3D engineered fibrin patch composed of UCBMSCs attenuated infarct-derived cardiac dysfunction when transplanted locally over a myocardial wound. Significance Ischemic heart failure (HF) is the end stage of many cardiovascular diseases, including myocardial infarction. The only definitive treatment for HF is cardiac transplant, which is hampered by limited number of heart donors and graft rejection. In recent times, cellular cardiomyoplasty has been expected to repair infarcted myocardium by implantation of different sources of stem or progenitor cells. However, low cell survival and myocardial implantation rates have motivated the emergence of novel approaches with the objective of generating graftable cell-based implants. Here, the potential of 3D engineered fibrin-umbilical cord blood-derived mesenchymal stem cells patches is shown to significantly recover lost general functions in post-infarcted mice.