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Drug response of scaffold-free cardiac constructs fabricated using bio-3D printing

Research Project

Project/Area Number 18K08763
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 55030:Cardiovascular surgery-related
Research InstitutionUniversity of Toyama (2020)
Saga University (2018-2019)

Principal Investigator

Arai Kenichi  富山大学, 医学部, 客員助教 (40752960)

Co-Investigator(Kenkyū-buntansha) 下戸 健  福岡工業大学, 情報工学部, 准教授 (40412457)
中山 功一  佐賀大学, 医学部, 教授 (50420609)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsバイオ3Dプリンタ / ヒトiPS細胞由来心筋細胞 / 組織工学 / スキャフォールドフリー / 薬理学 / 動物実験代替法 / 心筋組織工学 / ヒトiPS由来心筋細胞
Outline of Final Research Achievements

3D cardiac constructs fabricated using human induced pluripotent stem cell derived cardiomyocytes are useful for evaluating the cardiotoxicity and drug response to new drug. We previously reported the fabrication of scaffold-free 3D cardiac constructs using a bio-3D printer, which can load cardiac spheroids onto a needle array. In this study, we developed a method to measure the contractile force in order to evaluate the drug response in cardiac constructs. We measured the movement of needle tip upon contraction of cardiac constructs on needle array. In order to evaluate drug response, contractile properties of cardiac constructs were measured following treatment with isoproterenol, propranolol, blebbistatin and E-4031. As a result, the developed method can evaluate the contractile force and drug response of cardiac constructs.

Academic Significance and Societal Importance of the Research Achievements

医薬品、化粧品を開発する為には、動物実験が必要不可欠だが、動物とヒトの種差の違いから薬効が異なることが課題として挙げられており、ヒト細胞を用いた新しい動物実験代替法が強く望まれている。本研究で開発した手法は、3次元心筋組織体を作製する為に足場材料を使用していないこと、心筋組織体作製に用いる剣山の針を利用することで、収縮力を評価することが出来る為、収縮力に影響を及ぼす様な薬剤の薬理応答性を評価するのに有効だと考えている。医薬品販売に於いて、心毒性が開発中止の一番の要因になっていることから、本手法が確立出来れば、新薬開発に貢献できる為、社会的意義は非常に大きい。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (9 results)

All 2021 2020 2019 2018

All Journal Article (4 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 4 results,  Open Access: 4 results) Presentation (4 results) (of which Int'l Joint Research: 2 results) Book (1 results)

  • [Journal Article] Drug response analysis for scaffold-free cardiac constructs fabricated using bio-3D printer2020

    • Author(s)
      Arai Kenichi、Murata Daiki、Takao Shoko、Nakamura Anna、Itoh Manabu、Kitsuka Takahiro、Nakayama Koichi
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 8972-8972

    • DOI

      10.1038/s41598-020-65681-y

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 2-Cl-C.OXT-A stimulates contraction through the suppression of phosphodiesterase activity in human induced pluripotent stem cell-derived cardiac organoids.2019

    • Author(s)
      Kitsuka T, Itoh M, Amamoto S, Arai KI, Oyama J, Node K, Toda S, Morita S, Nishida T, Nakayama K.
    • Journal Title

      PLoS One

      Volume: 14 Issue: 7 Pages: 1-15

    • DOI

      10.1371/journal.pone.0213114

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Fabrication of scaffold-free tubular cardiac constructs using a Bio-3D printer.2018

    • Author(s)
      Arai K, Murata D, Verissimo AR, Mukae Y, Itoh M, Nakamura A, Morita S, Nakayama K
    • Journal Title

      PLoS One

      Volume: 13 Issue: 12 Pages: e0209162-e0209162

    • DOI

      10.1371/journal.pone.0209162

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The addition of human iPS cell-derived neural progenitors changes the contraction of human iPS cell-derived cardiac spheroids.2018

    • Author(s)
      Yosuke Mukae、Ryo Noguchi et al
    • Journal Title

      Tissue and Cell

      Volume: Available online 5 May 2018 Pages: 61-67

    • DOI

      10.1016/j.tice.2018.05.002

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Drug response of scaffold-free cardiac constructs fabricated using bio-3D printing2019

    • Author(s)
      Arai K, Murata D, Nakayama K
    • Organizer
      International Conference on Biofabrication
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] バイオ3Dプリンタにより作製した心筋組織体を用いた薬理応答性の検討2019

    • Author(s)
      荒井健一、村田大紀、中山功一
    • Organizer
      第18回日本再生医療学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] バイオ3Dプリンタにより作製した心筋組織体を用いた薬理応答性の検討2018

    • Author(s)
      荒井健一、村田大紀、中山功一
    • Organizer
      第18回 日本再生医療学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] Drug response of scaffold-free cardaic constructs fabricated using bio-3D printing2018

    • Author(s)
      Kenichi Arai, Daiki Murata, Koichi Nakayama
    • Organizer
      5th TERMIS World Congress
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Book] Bio-3D Printed Organs as Drug Testing Tools (Kenzan method for scaffold-free biofabrication)2021

    • Author(s)
      Arai K and Nakayama K
    • Total Pages
      184
    • Publisher
      Springer Nature
    • ISBN
      9783030586881
    • Related Report
      2020 Annual Research Report

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Published: 2018-04-23   Modified: 2022-01-27  

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