Abstract 16726: N-Cadherin Overexpression Improves the Reparative Potency of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes in Infarcted Mouse Hearts

Abstract

Background: Stem-cell-based therapy is a promising approach for the treatment of myocardial infarction (MI); however, the effectiveness of the treatment is believed to be limited by the poor survival and functional integration of transplanted cells. Within the heart, the adhesion between cardiomyocytes (CMs) is mediated by N-cadherin (CDH2), and CDH2 expression is well correlated with the efficacy of mesenchymal stem cells for myocardial repair. Thus, we determined whether the electrical connectivity, engraftment, and reparative potency of human induced-pluripotent stem-cell-derived cardiomyocytes (hiPSC-CMs) can be improved via CDH2 overexpression. Materials and methods: Conduction velocities were measured in cultured CDH2-overexpressing hiPSC-CMs (CDH2-CMs) and wild-type hiPSC-CMs (WT-CMs) via optical mapping. MI was induced in SCID mice via coronary artery ligation; then, the mice were treated with CDH2-CMs or WT-CMs (310 5 cells/mouse) (i.e., the MI+WT-CM and MI+WT-CM groups, respectively), or with neither experimental treatment (the MI group). The cells were injected directly into the infarcted region of the heart, cardiac function and infarct size were evaluated via post mortem examination, and the engraftment rate was evaluated histologically. Results: In-vitro conduction velocities were significantly greater (p<0.05) in CDH2-overexpressing hiPSC-CMs than in wild-type hiPSC-CMs, while in-vivo measurements of cardiac function (left-ventricular ejection fraction and fractional shortening), infarct size, and the hiPSC-CM engraftment/survival rate at week 4 after MI were significantly better in the MI+CDH2-CM group than in MI+WT-CM animals and in both cell-treatment groups than in MI animals . Conclusion: N-cadherin overexpression improves the electrical connectivity of cultured hiPSC-CMs, as well as the engraftment/survival and reparative potency of transplanted hiPSC-CMs in infarcted mouse hearts. Key words: N-cadherin, Myocardial Infarction, human induced pluripotent stem cells.