2023 Fiscal Year Final Research Report

Creation of 3D atrial and ventricular fields from human iPS cells by means of nanographene-cardiac ECM scaffold

Research Project

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Project/Area Number	21K12661
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 90110:Biomedical engineering-related
Research Institution	Yamagata University
Principal Investigator	Feng Zhonggang 山形大学, 大学院理工学研究科, 教授 (10332545)
Co-Investigator(Kenkyū-buntansha)	小沢田正山形大学, 大学院理工学研究科, 客員教授 (10143083) 佐藤大介山形大学, 大学院理工学研究科, 助教 (60536960)
Project Period (FY)	2021-04-01 – 2024-03-31
Keywords	３D高度機能的心筋組織の構築 / サブタイプ心筋細胞 / 心室・心房機能野 / 複合基質ナノグラフェン機能材料 / 心室ECM基質
Outline of Final Research Achievements	Through adsorption and release of functional factors on our flexible nano-graphene electrodes and application of dynamic strain and electrical stimulation in a bioreactor, we confirmed electrically induced migration of cardiomyocyte subtypes derived from human iPS cells while their differentiation and maturation. This contributed to the formation of atrial or ventricular myocardial tissue. A method for measuring the beating force under consideration of the dynamic characteristics of three-dimensional myocardial tissue made from porcine ventricular extracellular matrix was established, and the beating characteristics of atria and ventricles were analyzed. Furthermore, the influence of the formation of cardiomyocyte clusters on the beating force of 3-dimensional regenerated myocardial tissue was investigated, and it was suggested that the spontaneously asynchronous beating in atrial-dominant cell clusters could induce alike ectopic foci happening with atrial fibrillation.
Free Research Field	再生医療工学
Academic Significance and Societal Importance of the Research Achievements	現在、ヒトiPS細胞から分化した心筋細胞の臨床研究を心筋再生医療の大きな進展として注目されている。しかしながら、多種のサブタイプ心筋細胞の混在を解決するため、サブタイプ心筋細胞の“無損傷”的単離法は一つ重要な課題である。本研究は、より深層な心臓発生過程に関する「原始心臓管の自発的収縮律動とそれに伴う電気活動がサブタイプ心筋細胞の分化・成熟および定方向的な遊走にどのような影響を及ぼすのか」の問いをin vitroで3次元組織スケールにおいて検討した。その成果によってサブタイプ心筋の単離法や心筋疾患メカニズムおよび創薬モデルに関する有力な研究方法論として、学術的・社会的に多大な波及効果を有する。