シミズ　タツヤ   Shimizu Tatsuya   清水　達也    所属   医学研究科 医学研究科 (医学部医学科をご参照ください)    職種   教授
言語種別	英語
発表タイトル	Aligned Human iPS cell-derived Cardiac Tissue Improves the Systolic and Relaxation Function through Promoting Synchronous Cardiomyocyte Contraction
会議名	第85回日本循環器学会学術集会
学会区分	全国規模の学会
発表形式	口頭
講演区分	一般
発表者・共同発表者	Takuma Takada, SASAKI Daisuke, MATSUURA Katsuhisa, Miura Koichiro, Sakamoto Satoru, Homma Jun, SHIMIZU Tatsuya, Hagiwara Nobuhisa
発表年月日	2021/03/26
開催地 （都市, 国名）	奈良県(ハイブリット開催)
概要	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.