Discovery of Therapeutic Targets for Heart Failure with Preserved Ejection Fraction using CRISPR/Cas9 Technology and Human Pluripotent Stem Cells.

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K16030
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Kitani Tomoya 京都府立医科大学, 医学(系)研究科(研究院), 助教 (30842257)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: 心不全 / 心筋細胞 / 心筋線維芽細胞

Outline of Final Research Achievements

We succeeded in CRISPR screening using human cardiomyocytes derived from pluripotent stem cells and identified promising candidate genes which could contribute to the development of heart failure due to diastolic dysfunction. However, we also found that stable cultivation of cardiac fibroblasts induced from pluripotent stem cells was difficult and further optimization is necessary. The candidate genes obtained in this study included genes that have not been reported to be involved in the pathogenesis of heart failure, which could be novel targets for future research to develop novel treatments for heart failure due to diastolic dysfunction.

Free Research Field

循環器疾患

Academic Significance and Societal Importance of the Research Achievements

本邦を含めて全世界的に社会の高齢化に伴う心不全患者の増加が予想されており、新たな心不全治療の開発は急務である。しかし、高齢者の心不全の主体である拡張不全型心不全に有効な治療法は未だ確立しておらず、その病態も不明な点が数多く残されている。本研究ではヒト多能性幹細胞より心臓構成細胞を作出し、CRISPR/Cas9システムを用いた遺伝子ノックアウトスクリーニングを行い、拡張不全型心不全の病態に寄与する遺伝子の候補の探索を実施した。本研究により将来の治療標的候補となりうる分子機序を解明する研究を実施する上で極めて重要な情報が得られたことから、学術的社会的意義に富む結果が得られた。