Development of heart-lung organoid generation technology using pluripotent stem cells

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K06652
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 44020:Developmental biology-related
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Lee Jiyoung 東京医科歯科大学, 統合研究機構, 非常勤講師 (20402860)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 心臓オルガノイド / 多能性幹細胞

Outline of Final Research Achievements

In this study, we generated human ESCs-derived heart organoids with high morphological similarity of in vivo heart, by adding BMP10 expressed in the fetal heart. The human heart organoids expressed cardiomyocyte markers, and the integral proteins of gap junctions and ion channels. Also, Na and Ca currents were detected in human heart organoids by patch clamp analysis. Moreover, a PORCN inhibitor (C59) and fatty acids were effective in the maturation of cardiomyocytes in human heart organoids. For the quantitative analysis of trabeculation in heart organoids, we developed a method using imaging analysis with a machine learning model after tissue clearing. The evaluation system of human heart organoids will be a useful tool for cardiac safety assessment of newly developed drugs. For the generation of heart-lung organoids from human pluripotent stem cells, we found that ROCK inhibitor plays an important role for the development of lung by interfering with the function of FGF signals.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

作製されたヒト心臓オルガノイドは心筋細胞マーカーの発現、NaとCaイオンチャネルタンパク質を持つだけではなく、NaとCa電流が確認され、各電流のパターンは生体の心臓に極めて似ていることが明らかとなった。その他にもHERGやIK1チャネルの発現が確認されたことからヒトES由来心臓オルガノイドは心臓の電気生理学的性質を総合的に再構築したものであると考えられる。これらの心臓オルガノイドと評価系を用いることで、将来的に薬剤毒性評価やdrug screeningに有効に活用できると考えられる。また、肺オルガノイドにおいても薬剤毒性評価系などの構築ができると予想されるため、医療への貢献が期待される。