Next generation in vitro tissue/organ models with 3D tissue from stem cells

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K19676
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Organ-based internal medicine and related fields
• Research Institution: Kyoto University
• Principal Investigator: Yamashita Jun 京都大学, iPS細胞研究所, 教授 (50335288)
• Research Collaborator: Kawatou Masahide
• Project Period (FY): 2017-06-30 – 2019-03-31
• Keywords: 疾患モデル / 細胞・組織 / 循環器・高血圧 / iPS細胞 / 不整脈

Outline of Final Research Achievements

1) In vitro reentry type arrhythmia model with human iPS cell-derived cardiac tissue sheets (hiPS-CTS): We generated mini-3D cardiac structure with human iPS cell-derived cardiac cells (cardiomyocytes and mesenchymal cells). Addition of E4031 induced QT prolongation as well as occurrence of ventricular tachycardia-like reentry arrhythmia.
2) Torsade de Pointes (TdP) model with hiPS-CTS: Addition of E4031 to hiPS-CTS induced TdP-like arrhythmia with polymorphic extracellular field potential and meandering of the center of reentry. This is the first in vitro TdP model, reported in Nature Communications.

Free Research Field

幹細胞生物学、循環器内科学、再生医学

Academic Significance and Societal Importance of the Research Achievements

TdPなどの致死性不整脈は、種々の疾患や薬剤の副作用に認められ重篤な結果をもたらす。しかしこれらを培養下に再現し、病態の検討を行えるin vitroモデルは存在しなかった。本研究は、ヒトiPS細胞由来の複数種の心臓の細胞を用いて３D構造を形成することにより、世界で初めてTdPの発生をin vitroで再現することに成功したものであり、今後の病態研究、創薬、安全性試験などに多大な貢献をもたらすと考えられる。