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Development of mature iPSC cardiomyocytes toward drug development

Research Project

Project/Area Number 21H02634
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 47040:Pharmacology-related
Research InstitutionNational Institute of Health Sciences

Principal Investigator

Kanda Yasunari  国立医薬品食品衛生研究所, 薬理部, 部長 (70510387)

Co-Investigator(Kenkyū-buntansha) 細田 洋司  信州大学, 学術研究院医学系, 准教授 (40359807)
芦原 貴司  滋賀医科大学, 医学部, 教授 (80396259)
朝倉 宏  国立医薬品食品衛生研究所, 食品衛生管理部, 部長 (40370936)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2023: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2022: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2021: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Keywords新型コロナウイルス / 後遺症 / ヒトiPS細胞 / 収縮 / 感染 / 次世代シークエンス / パスウエイ解析 / ミトコンドリア / イメージング / ミトコンドリア毒性 / ウイルス感染 / SARS-CoV-2 / 心筋 / iPS / 成熟化 / 機能的毒性 / 新興感染症 / ドラッグリポジショニング / 器質的毒性 / iPS心筋 / 不整脈 / iPS細胞 / 配向性 / COVID-19
Outline of Research at the Start

新型コロナウイルス感染症により不整脈などが報告されており、医学的にも社会的にも喫緊の問題である。そこで本研究では、成熟したヒトiPS細胞由来心筋細胞を用いて、新型コロナウイルスSARS-CoV-2の感染による心筋障害メカニズムを検討する。次に、既存の医薬品を用いて、ウイルス感染による心筋障害を回復できる化合物を探索する。以上の研究により、新型コロナウイルス感染症の心筋障害に関する病態を解明し、治療薬の技術基盤を構築することが期待される。

Outline of Final Research Achievements

Although therapeutic agents against COVID-19 have been developed, treatments for long COVID, such as hear failure, have not yet been established. We found that mitochondrial toxicity is involved in contraction dysfunction and structural toxicity caused by SARS-CoV-2 infection, suggesting the pathological mechanism related to long-term COVID-19 symptoms, such as heart failure. Thus, development of new therapeutic agents would be expected in the future.

Academic Significance and Societal Importance of the Research Achievements

新型コロナウイルス感染症(COVID-19)に対する治療薬の開発は進められているが、臓器障害や長期症状に対する治療法は未だ確立されていない。本研究により、SARS-CoV-2感染による心筋障害にミトコンドリア毒性が関与していることが示唆されたことから、COVID-19の心不全などの長期症状に関する病態メカニズムの一端を明らかにできた。今後、新たな治療薬の開発などにつながることが期待される。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • Research Products

    (42 results)

All 2024 2023 2022 2021

All Journal Article (9 results) (of which Peer Reviewed: 9 results,  Open Access: 8 results) Presentation (33 results) (of which Int'l Joint Research: 10 results,  Invited: 11 results)

  • [Journal Article] Drug development using human iPSC-derived cardiomyocytes and future perspectives2024

    • Author(s)
      Kawagishi H, Yanagida S, Kanda Y.
    • Journal Title

      Comprehensive Toxicology, Fourth Edition (Elsevier)

      Volume: -

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] SARS-CoV-2 causes dysfunction in human iPSC-derived brain?microvascular endothelial cells potentially by modulating the Wnt signaling pathway2024

    • Author(s)
      Yamada Shigeru、Hashita Tadahiro、Yanagida Shota、Sato Hiroyuki、Yasuhiko Yukuto、Okabe Kaori、Noda Takamasa、Nishida Motohiro、Matsunaga Tamihide、Kanda Yasunari
    • Journal Title

      Fluids and Barriers of the CNS

      Volume: 21 Issue: 1 Pages: 32-32

    • DOI

      10.1186/s12987-024-00533-9

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] TRPC3-Nox2 Protein Complex Formation Increases the Risk of SARS-CoV-2 Spike Protein-Induced Cardiomyocyte Dysfunction through ACE2 Upregulation.2022

    • Author(s)
      Kato Y, Nishiyama K, Man Lee J, Ibuki Y, Imai Y, Noda T, Kamiya N, Kusakabe T, Kanda Y, Nishida M.
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 24 Issue: 1 Pages: 102-102

    • DOI

      10.3390/ijms24010102

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] SARS-CoV-2 induces barrier damage and inflammatory responses in the human iPSC-derived intestinal epithelium2022

    • Author(s)
      Yamada S, Noda T, Okabe K, Yanagida S, Nishida M, Kanda Y.
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 149 Issue: 3 Pages: 139-146

    • DOI

      10.1016/j.jphs.2022.04.010

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Drug repurposing for the treatment of COVID-192022

    • Author(s)
      Kato Y, Nishiyama K, Nishimura A, Noda T, Okabe K, Kusakabe T, Kanda Y, Nishida M.
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 149 Issue: 3 Pages: 108-114

    • DOI

      10.1016/j.jphs.2022.04.007

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Lysophosphatidic Acid Promotes the Expansion of Cancer Stem Cells via TRPC3 Channels in Triple-Negative Breast Cancer2022

    • Author(s)
      Hirata Naoya、Yamada Shigeru、Yanagida Shota、Ono Atsushi、Yasuhiko Yukuto、Nishida Motohiro、Kanda Yasunari
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 23 Issue: 4 Pages: 1967-1967

    • DOI

      10.3390/ijms23041967

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of alveolar and airway cells from human iPS cells: toward SARS-CoV-2 research and drug toxicity testing2021

    • Author(s)
      Kayoko Tsuji, Shigeru Yamada, Kazuya Hirai, Hiroshi Asakura, Yasunari Kanda
    • Journal Title

      The Journal of Toxicological Sciences

      Volume: 46 Issue: 9 Pages: 425-435

    • DOI

      10.2131/jts.46.425

    • NAID

      130008082554

    • ISSN
      0388-1350, 1880-3989
    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Chronic cardiotoxicity assessment of BMS-986094, a guanosine nucleotide analogue, using human iPS cell-derived cardiomyocytes2021

    • Author(s)
      Shota Yanagida, Ayano Satsuka, Sayo Hayashi, Atsushi Ono, Yasunari Kanda
    • Journal Title

      The Journal of Toxicological Sciences

      Volume: 46 Issue: 8 Pages: 359-369

    • DOI

      10.2131/jts.46.359

    • NAID

      130008070942

    • ISSN
      0388-1350, 1880-3989
    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comprehensive Cardiotoxicity Assessment of COVID-19 Treatments Using Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes2021

    • Author(s)
      Shota Yanagida, Ayano Satsuka, Sayo Hayashi, Atsushi Ono, Yasunari Kanda
    • Journal Title

      Toxicol Sci

      Volume: 183 Issue: 1 Pages: 227-239

    • DOI

      10.1093/toxsci/kfab079

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] ワクチン・アジュバントの安全性評価2024

    • Author(s)
      諫田泰成
    • Organizer
      第2回近未来ワクチンフォーラム
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] ヒトiPS細胞由来脳微小血管内皮様細胞のバリア機能に対するSARS-CoV-2感染の影響2023

    • Author(s)
      柳田翔太, 山田茂, 坡下真大, 佐藤寛之, 安彦行人, 岡部馨, 野田隆正, 西田基宏, 松永民秀, 諫田泰成
    • Organizer
      フォーラム2023 衛生薬学・環境トキシコロジー
    • Related Report
      2023 Annual Research Report
  • [Presentation] SARS-CoV-2感染によるヒト血液脳関門のバリア機能低下2023

    • Author(s)
      山田茂, 坡下真大, 柳田翔太, 佐藤寛之, 安彦行人, 岡部馨, 野田隆正, 松永民秀, 西田基宏, 諫田泰成
    • Organizer
      第148回日本薬理学会関東部会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 医薬品開発における動物実験代替法の考え方とFDA近代化法2.02023

    • Author(s)
      諫田泰成
    • Organizer
      第57回日本動物実験技術者協会総会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] ヒトiPS 細胞由来心筋細胞の薬理評価と疾患モデルへの展開2023

    • Author(s)
      諫田泰成
    • Organizer
      第32回日本循環薬理学会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] パンデミックの不確実性と創薬2023

    • Author(s)
      諫田泰成
    • Organizer
      第35回 自然科学研究機構シンポジウム
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] Development of cardiotoxicity testing using iPSC cardiomyocytes2022

    • Author(s)
      Yasunari Kanda
    • Organizer
      SAAE-I annual meeting
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Development of SARS-CoV-2 infection model using human iPSC2022

    • Author(s)
      Yasunari Kanda
    • Organizer
      The 21st International Congress of the European Society of Toxicology In Vitro
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Development of in vitro cardiotoxicity assessment using human iPS cell technology.2022

    • Author(s)
      Yasunari Kanda, Sae Hayashi, Ayano Satsuka
    • Organizer
      The 21st International Congress of the European Society of Toxicology In Vitro
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Current status and future perspectives of toxicity testing using stem cell-derived 3D models2022

    • Author(s)
      Yasunari Kanda
    • Organizer
      ICT2022
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Contractility assessment of human iPSC-derived cardiomyocytes using electrical cell-substrate impedance and imaging-based cell motion vector systems2022

    • Author(s)
      Satsuka A, Hayashi S, Yanagida S, Ono A, Hayakawa T, Matsukawa H, Kanda Y
    • Organizer
      Safety Pharmacology Society Annual Meeting
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Development of SARS-CoV-2 infection model using human iPSC-derived cardiomyocytes2022

    • Author(s)
      Satsuka A, Yamada S, Yanagida S, Hayashi S, Asakura H, Nishida M*1,2, Kanda Y
    • Organizer
      24th Japan-Korea Joint Seminar on Pharmacology
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] COVID-19の病態メカニズムに基づく創薬への展開2022

    • Author(s)
      諫田泰成, 西田基宏
    • Organizer
      第96回日本薬理学会年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 配向性を有するヒトiPS細胞由来心筋細胞の収縮評価2022

    • Author(s)
      佐塚文乃,林紗代,柳田翔太,小野敦,諫田泰成
    • Organizer
      第96回日本薬理学会年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] ヒトiPS細胞由来小腸上皮細胞を用いたSARS-CoV-2感染モデルの開発2022

    • Author(s)
      山田茂, 野田隆政, 岡部かおり, 柳田翔太, 西田基宏, 諫田泰成
    • Organizer
      第96回日本薬理学会年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] ヒト iPS 細胞由来分化細胞を用いた SARS-CoV-2 感染モデルの開発2022

    • Author(s)
      諫田泰成
    • Organizer
      第49回日本毒性学会学術年会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] ヒトiPS細胞由来心筋細胞におけるElectro-mechanical windowを用いた催不整脈評価2022

    • Author(s)
      柳田 翔太、佐塚 文乃、林 紗代、小野 敦、諫田 泰成
    • Organizer
      日本薬学会第142年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] ヒトiPS細胞技術を活用したCOVID-19治療薬の薬理評価2022

    • Author(s)
      諫田 泰成
    • Organizer
      第95回薬理学会年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] ヒトiPS細胞由来心筋細胞を用いたBCR-ABLチロシンキナーゼ阻害薬の慢性毒性評価2022

    • Author(s)
      佐塚 文乃、林 紗代、柳田 翔太、諫田 泰成
    • Organizer
      第95回薬理学会年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] ヒトiPS細胞由来心筋細胞を用いたBMS-986094による慢性収縮毒性2022

    • Author(s)
      柳田 翔太、佐塚 文乃、林 紗代、小野 敦、諫田 泰成
    • Organizer
      第95回薬理学会年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] ヒトiPS細胞由来分化細胞を用いた新型コロナウイルスの感染モデルの開発2022

    • Author(s)
      諫田 泰成
    • Organizer
      第21回日本再生医療学会総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Current challenges and future perspectives of safety pharmacology testing using new approach methodologies2022

    • Author(s)
      諫田 泰成
    • Organizer
      第13回日本安全性薬理研究会学術年会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] ヒトiPS細胞を用いた創薬の現状と今後の展望2021

    • Author(s)
      諫田 泰成
    • Organizer
      再生医療 EXPO
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] ヒトiPS細胞由来心筋細胞を用いたCOVID-19治療薬の評価2021

    • Author(s)
      佐塚文乃、山田 茂、柳田翔太、小野 敦、朝倉 宏、加藤百合、西山和宏、西田基宏、諫田泰成
    • Organizer
      筋生理の集い
    • Related Report
      2021 Annual Research Report
  • [Presentation] ヒトiPS細胞を活用した抗がん剤心毒性の現状と今後の展望2021

    • Author(s)
      諫田 泰成
    • Organizer
      第4回日本腫瘍循環器学会学術集会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Proarrhythmia Risk Assessment by Electro-mechanical Window in Human iPS Cell-derived Cardiomyocytes2021

    • Author(s)
      Shota Yanagida, Ayano Satsuka, Sayo Hayashi, Atsushi Ono, Yasunari Kanda
    • Organizer
      Safety Pharmacology Society
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] iPSC Model for Safety Testing of COVID Therapies2021

    • Author(s)
      Yasunari Kanda
    • Organizer
      Safety Pharmacology Society
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] SARS-CoV-2感染による心筋障害モデルの開発とCOVID-19治療薬の心毒性リスク評価2021

    • Author(s)
      柳田翔太,佐塚文乃,山田 茂、林紗代,小野敦,諫田泰成
    • Organizer
      フォーラム2021衛生薬学・環境トキシコロジー
    • Related Report
      2021 Annual Research Report
  • [Presentation] 抗がん剤心毒性の評価法の開発と標準化2021

    • Author(s)
      諫田 泰成
    • Organizer
      レギュラトリーサイエンス学会 第11回学術大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] ヒトiPS細胞由来心筋細胞を用いた慢性収縮毒性評価法の開発2021

    • Author(s)
      柳田翔太,佐塚文乃,林紗代,小野敦,諫田泰成
    • Organizer
      レギュラトリーサイエンス学会 第11回学術大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] ヒトiPS細胞由来心筋細胞を用いた収縮毒性評価法の開発2021

    • Author(s)
      柳田翔太、佐塚文乃、林紗代、小野敦、諫田泰成
    • Organizer
      第7回次世代を担う若手のためのレギュラトリーサイエンスフォーラム
    • Related Report
      2021 Annual Research Report
  • [Presentation] Proarrhythmia risk assessment using electro-mechanical window in human iPS cells-derived cardiomyocytes2021

    • Author(s)
      Shota Yanagida, Ayano Satsuka, Sayo Hayashi, Atsushi Ono, Yasunari Kanda
    • Organizer
      The 23rd Korea-Japan Joint Seminar on Pharmacology
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Drug repurposing for SARS-COV-2 infection via ACE2 internalization in iPSC cardiomyocytes2021

    • Author(s)
      Kayoko Tsuji, Shigeru Yamada, Yuri Kato, Motohiro Nishida, Yasunari Kanda
    • Organizer
      ISSCR 2021
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research

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Published: 2021-04-28   Modified: 2025-01-30  

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