ヤマグチ　ジユンイチ   YAMAGUCHI Jiyun'ichi   山口　淳一    所属   医学部 医学科（東京女子医科大学病院）    職種   教授・基幹分野長
言語種別	日本語
発表タイトル	Fibroblast alignment control regulates cardiomyocyte alignment in the bioengineered cardiac tissue
会議名	第87回日本循環器学会学術集会
学会区分	国際学会及び海外の学会
発表形式	口頭
講演区分	一般
発表者・共同発表者	◎飯田達郎, 松浦勝久, 高橋宏信, 髙田卓磨, 小池俊晴, 山口淳一, 清水達也
発表年月日	2023/03/12
国名	日本
開催地 （都市, 国名）	福岡
開催期間	2023/03/10～2023/03/12
概要	Background: Although the native heart is composed of several layered tissues with aligned cardiomyocytes, regulatory mechanisms of cardiomyocyte alignment are not still understood. Recently we have reported that human-iPS cell-derived cardiomyocytes (hiPSC-CMs) cultured on the micro-processed fibrin-gel showed an aligned structure and improved the systolic and relaxation function through the unidirectional and synchronous contraction. The heart is composed of various types of cells including fibroblasts. Although mutual interactions between cardiomyocytes and fibroblasts have been reported, it remains unclear whether fibroblasts regulate cardiomyocyte alignment. Method/Result: Acrylamide was photopolymerized on a temperature-responsive culture dish to create a stripe-shaped pattern culture surface for alignment control. Although hiPSC-CMs showed still random orientation when cultured on it, human fibroblasts showed fine unidirectional alignment. Next, we examined whether fibroblast alignment regulated cardiomyocyte alignment. When hiPSC-CMs were cultured on the aligned fibroblasts, cardiac troponin T-positive cardiomyocytes were observed in the orientation of fibroblast orientation. Furthermore, when a cardiac cell sheet composed of cardiomyocytes with random orientation was layered on the aligned fibroblast, cardiomyocytes were also observed in a parallel direction with the fibroblast orientation and the coherency, which is orientation intensity, was significantly higher in cardiomyocytes on aligned fibroblast than those on non- aligned fibroblasts (0.466±0.087 vs. 0.086±0.032, p=0.015, N=3). Moreover, live imaging using AAV-GFP-infected hiPSC-CMs revealed that almost all of the cardiomyocytes were aligned within a few days after layering on aligned fibroblasts. Conclusion: Fibroblast alignment might directly regulate cardiomyocyte alignment. These findings will lead to fabricating the functional bioengineered cardiac tissue and understanding the molecular mechanisms of cardiomyocyte alignment control in the heart.