Nobuhisa Hagiwara    Department   Other, Other    Position
Language	English
Title	Aligned Human iPS cell-derived Cardiac Tissue Improves the Systolic and Relaxation Function through Promoting Synchronous Cardiomyocyte Contraction
Conference	第85回日本循環器学会学術集会
Conference Type	Nationwide Conferences
Presentation Type	Speech
Lecture Type	General
Publisher and common publisher	Takuma Takada, SASAKI Daisuke, MATSUURA Katsuhisa, Miura Koichiro, Sakamoto Satoru, Homma Jun, SHIMIZU Tatsuya, Hagiwara Nobuhisa
Date	2021/03/26
Venue (city and name of the country)	奈良県(ハイブリット開催)
Summary	Introduction: Native myocardium is composed of several layers of aligned cardiac tissue. However, the meaning of cardiomyocyte alignment control for contractile properties remains elusive. The aims of our study are to evaluate the effect of alignment control on contractile properties of hiPS-derived cardiac tissues and its underlying mechanisms.Methods and Results: The micro-processed fibrin gel with inversed micro V shaped ridges (VFG) was generated. Human iPS cell-derived cardiomyocytes (hiPS-CMs) were seeded on VFG or flat-surface fibrin gel (control). When cardiomyocytes alignment was elucidated with Phalloidin staining and Fourier analysis, the orientation index was significantly higher on VFG than control (1.5±0.1 vs. 1.2±0.1, p<0.001, n=4), suggesting that hiPS-CMs were aligned more uniformly on VFG than control. The analysis using the contractile force measurement system revealed that several functional properties including contractile force, maximum contractile and relaxation velocity were significantly increased in VFG group compared with those in control group under the electrical stimulation [contractile force (75ppm): 0.9±0.5 mN vs. 0.5±0.3 mN, p=0.02, n=11]. Moreover, relaxation function was further increased with isoproterenol treatment in VFG group, suggesting that cardiac tissue functional maturation might be promoted in alignment control. When time phases of contraction at multiple points in cardiac tissues were examined through motion capture analysis, cardiomyocytes on VFG showed more synchronous contraction than those on control. There was no significant difference in glucose consumption between the two groups. Conclusions: Aligned human cardiac tissue improves the systolic and relaxation function. Further, understanding the molecular mechanism of alignment control-mediated synchronous contraction of cardiomyocytes might provide us the new insights on heart homeostasis and heart failure.