Abstract 12305: Cardiomyocyte Alignment Control Promotes the Electrical Integration and Improve the Contractile Function of Human Cardiac Tissue

Abstract

Introduction: Alignment, as seen in the native myocardium, is crucial for maintaining the functional cardiac tissue. However, it remains unclear how cardiomyocyte alignment control influences cardiac function and the underlying mechanisms. The aims of our study were to fabricate aligned human cardiac tissue using a micro-processed fibrin gel and elucidated the effect of alignment control on contractile properties. Methods: We fabricated aligned human cardiac tissue through cultivating human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) on a micro-processed fibrin gel with inverted V-shaped ridges (MFG). The orientation index was calculated based on the Fourier analysis using Phalloidin staining images. The cardiac tissue function was evaluated with a contractile force measurement system. Results: The orientation index of hiPSC-CMs on MFG was significantly higher than that on the control fibrin gel (1.5±0.1 vs. 1.2±0.1, p<0.001, n=4) and that was close to the orientation index of an adult rat heart tissue (1.6±0.1), suggesting hiPSC-CMs on MFG were aligned more uniformly than the control. The contractile force, maximum contractile velocity, and relaxation velocity were significantly increased in aligned cardiac tissue compared with non-aligned cardiac tissue [contractile force (75bpm): 0.9±0.5 mN vs. 0.5±0.3 mN, p=0.02, n=11]. Motion capture analysis revealed cardiomyocytes in the aligned cardiac tissues showed more unidirectional contraction than the non-aligned cardiac tissues. Furthermore, the timing of contraction at five designated points in the tissues was significantly closed in the aligned tissue, suggesting cardiomyocyte alignment control might improve the systolic and relaxation function of cardiac tissue by promoting synchronous cardiomyocyte contraction. Conclusion: Cardiomyocyte alignment control promoted the electrical integration of cardiomyocytes and contributed to generate the strong contractile force. Understanding the molecular mechanisms of alignment control-mediated synchronous contraction of cardiomyocytes might provide us the new insights on electrophysiological properties of heart tissue.