Exploration of novel in vitro lethal arrhythmia models with 3D tissues from human iPS cells
| Project/Area Number |
18H04048
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Medium-sized Section 53: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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| Co-Investigator(Kenkyū-buntansha) |
佐藤 守俊 東京大学, 大学院総合文化研究科, 教授 (00323501)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥44,070,000 (Direct Cost: ¥33,900,000、Indirect Cost: ¥10,170,000)
Fiscal Year 2020: ¥14,170,000 (Direct Cost: ¥10,900,000、Indirect Cost: ¥3,270,000)
Fiscal Year 2019: ¥14,170,000 (Direct Cost: ¥10,900,000、Indirect Cost: ¥3,270,000)
Fiscal Year 2018: ¥15,730,000 (Direct Cost: ¥12,100,000、Indirect Cost: ¥3,630,000)
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| Keywords | ヒトiPS細胞 / 病態モデル病 / 病態解析 / 不整脈 / 3次元組織 / 病態モデル / ３次元組織 |
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| Outline of Final Research Achievements |
Lethal arrhythmias often lead to sudden death. To date, it has been impossible to reproduce the occurrence of these arrhythmias in vitro. Recently, we have succeeded in reproducing a lethal arrhythmia called Torsade de Pointes (TdP) using human iPS cell-derived cardiac tissue sheets (Nat Commun, 2017). That is considered to be the first in vitro model of TdP. In this study, we further tried to reproduce other lethal arrhythmias, including ventricular fibrillation (VF). We examined various additional conditions to our TdP model, and now we are finding a condition to induce VF-like phenomena in vitro. These findings would be extensively applied to pathogenesis analysis of VF, drug discovery, drug safety tests, and so on.
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| Academic Significance and Societal Importance of the Research Achievements |
ヒトの不整脈を培養下に再現し、病態を解析したり治療法を探索したりする方法はこれまでありませんでした。また薬剤安全性試験においても細胞を使って危険性を推測するにとどまっていました。本研究は、心筋細胞だけでなく、複数種類の心臓の細胞を誘導し、さらにそれを3次元的組織に作り上げることにより、実際の不整脈において起こっている病態生理に近い状態を作り出したものであり、世界初のTdPモデルさらには世界初の心室細動モデルとなる研究で、その学術的意義は大変に大きい。また突然死に至る致死性不整脈に対して種々の解析が可能となり将来の治療応用等社会的意義も非常に大きいと考えられます。
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Report
(4 results)
Research Products
(20 results)
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[Journal Article] Induced Pluripotent Stem Cells and Their Use in Human Models of Disease and Development.2019
Author(s)
Karagiannis P, Takahashi K, Saito M, Yoshida Y, Okita K, Watanabe A, Inoue H, Yamashita JK, Todani M, Nakagawa M, Osawa M, Yashiro Y, Yamanaka S, Osafune K.
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Journal Title
Physiol Rev
Volume: 99
Issue: 1
Pages: 78-114
DOI
Related Report
Peer Reviewed
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