2021 Fiscal Year Final Research Report

Research of disease modeling and drug discovery through the maturation regulation of human iPS cell-derived cardiac tissue recapitulating human heart function

Research Project

PDF

Project/Area Number	19K09281
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 55030:Cardiovascular surgery-related
Research Institution	Institute of Physical and Chemical Research
Principal Investigator	Masumoto Hidetoshi 国立研究開発法人理化学研究所, 生命機能科学研究センター, 上級研究員 (70645754)
Co-Investigator(Kenkyū-buntansha)	川東正英京都大学, 医学研究科, 助教 (00837700) 湊谷謙司京都大学, 医学研究科, 教授 (20393241) 武田匡史京都大学, 医学研究科, 客員研究員 (40547501)
Project Period (FY)	2019-04-01 – 2022-03-31
Keywords	iPS細胞 / 心臓再生医療
Outline of Final Research Achievements	We established the method to efficiently induce cardiomyocytes and endothelial cells from human iPS cells through the regulation of canonical Wnt signaling and to stably generate self-pulsating engineered heart tissues. To investigate the tissue maturation, we stimulated the tissues with dynamic fluidic culture which confered significant thickening of cardiomyocyte layer and responsibility against external electrical stimulation and drug administration. We also found that the stimulation forms vascular network inside of the tissue. Using Organ-on-a-Chip technology, we developed a system to evaluate tissue function with high sensitivity. We started to culture familial dilated cardiomyopathy patient-derived iPS cells and succeeded in preparing cell bank and cardiovascular cell diferentiation which enabled us to generate disease-specific iPS cell-derived cardiac tissue which contributes to disease modeling and drug discovery.
Free Research Field	心臓血管外科学
Academic Significance and Societal Importance of the Research Achievements	末期心不全で心臓移植以外に治療法がないものの、ドナー不足のため救命し得ない患者に対する新たな治療スキームが模索し続けられてきた。本研究開発により実現した、心臓病患者由来iPS細胞から作製した、成熟化を伴う生体模倣性人工心臓組織は疾患再現・創薬研究に大きく貢献しうると考えられ、高い社会的意義を有する。本研究は我々の有する独自のヒトiPS細胞から作製した人工心臓組織を有効活用し、実臨床におけるニーズを解決することに照準を合わせた、トランスレーショナル・リサーチ（橋渡し研究）の好例と言え、高い学術的意義を有する。