Elucidation of the pathophysiology of heart failure with human cardiac spheroid/organoid

2021 Fiscal Year Final Research Report

• Project/Area Number: 19H03660
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Keio University
• Principal Investigator: FUJITA Jun 慶應義塾大学, 医学部(信濃町), 講師(非常勤) (10306706)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: ヒトiPS細胞 / 心筋スフェロイド / 人工心筋組織 / Engineered Heart Tissue

Outline of Final Research Achievements

The matured and high-quality artificial myocardial tissues are successfully produced with human iPS cell-derived cardiomyocytes. The appropriate drug response is confirmed, and a platform for the development of next-generation therapeutic agents is established for heart failure. In addition, high-quality cardiac spheroids are generated with human iPS cell-derived cardiomyocytes. It is revealed that cardiac spheroids become mature after transplantation, and the process of maturation is clarified. It is also confirmed that cardiac spheroids produce VEGF. The transplanted cardiac spheroids promote angiogenesis, and they are engrafted and matured in the failing hearts. These results elucidate the state of the transplanted cardiac tissue in the heart failure.

Free Research Field

循環器内科

Academic Significance and Societal Importance of the Research Achievements

本研究ではin vitroにおいて成熟化した高品質な人工心筋組織を作製することで詳細な心不全の病態解析および薬物開発を可能にした。また、in vivoで移植された心筋組織が生着、成熟化する機序が明らかになった。本研究によって得られた人工心筋組織の基盤技術は国際的にもトップクラスである。これらの成果によりヒトiPS細胞由来の人工心筋組織を用いた心不全の病態解析および創薬、心筋スフェロイドを用いた心不全治療は飛躍的に進歩すると考えられる。次世代の創薬開発に果たす役割は大きく国内外の循環器領域におけるインパクトは極めて大きい。