| Project/Area Number |
17K19676
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Organ-based internal medicine and related fields
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| Research Institution | Kyoto University |
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Principal Investigator |
Yamashita Jun 京都大学, iPS細胞研究所, 教授 (50335288)
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| Research Collaborator |
Kawatou Masahide
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| Project Period (FY) |
2017-06-30 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2017: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
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| Keywords | 疾患モデル / 細胞・組織 / 循環器・高血圧 / iPS細胞 / 不整脈 / 再生医学 |
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| 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.
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| 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。
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