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Development of cardiomyopathy-specific iPS cell-derived 3-dimensional biomaterial-based cardiac tissues suitable for drug discovery

Research Project

Project/Area Number 16K10626
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Cardiovascular surgery
Research InstitutionInstitute of Physical and Chemical Research (2017-2018)
Kyoto University (2016)

Principal Investigator

Masumoto Hidetoshi  国立研究開発法人理化学研究所, 生命機能科学研究センター, 上級研究員 (70645754)

Co-Investigator(Kenkyū-buntansha) 池田 義  京都大学, 医学研究科, 准教授 (40281092)
南方 謙二  京都大学, 医学研究科, 講師 (60539675)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords心臓再生医療 / iPS細胞 / バイオエンジニアリング / 心筋疾患外科学 / 拡張型心筋症 / 再生医学 / 創薬研究 / バイオマテリアル
Outline of Final Research Achievements

First, we have established a protocol for cardiac cell differentiation from cardiomyopathy-specific iPS cells which is essential for the cell preparation of cardiomyopathy-specific iPS cell-derived 3-dimensional biomaterial-based cardiac tissues. Next, we constructed various types of 3-dimensional cardiac tissues and analysed them which resulted in immature tissue property and function including ion channel expression. We loaded the tissues with electrical stimulation training culture which promoted the tissue maturation which was confirmed by the expression level of mRNAs relating to tissue maturation. Here, we established a technological basis for the development of cardiomyopathy-specific iPS cell-derived 3-dimensional biomaterial-based cardiac tissues suitable for drug discovery.

Academic Significance and Societal Importance of the Research Achievements

本邦においては、今後心不全患者の増加が予想されている一方で、心臓移植や植込み型人工心臓は未だ十分な供給がなされない状況がある。本研究成果は、心不全患者に対する創薬研究における、iPS細胞を用いた新たな技術基盤を与えるものであり、ヘルスケアおよび医療経済に対し貢献しうるものである。また、心筋症患者iPS細胞由来成熟化人工心臓組織は、疾患の病態をin vitroで再現しうるものであり、疾患進行に関してこれまで動物実験などで得られなかった新たな学術的発見をもたらすのに貢献するものである。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (33 results)

All 2019 2018 2017 2016 Other

All Journal Article (11 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 11 results,  Open Access: 8 results,  Acknowledgement Compliant: 2 results) Presentation (20 results) (of which Int'l Joint Research: 9 results,  Invited: 4 results) Book (1 results) Remarks (1 results)

  • [Journal Article] Chronic optical pacing conditioning of h-iPSC engineered cardiac tissues.2019

    • Author(s)
      Dwenger M, Kowalski WJ, Ye F, Yuan F, Tinney JP, Setozaki S, Nakane T, Masumoto H, Campbell P, Guido W, Keller BB.
    • Journal Title

      J Tissue Eng

      Volume: 10 Pages: 204173141984174-204173141984174

    • DOI

      10.1177/2041731419841748

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Human iPS cell-engineered three-dimensional cardiac tissues perfused by capillary networks between host and graft.2018

    • Author(s)
      Masumoto H, Yamashita JK.
    • Journal Title

      Inflamm Regen.

      Volume: 38 Issue: 1 Pages: 26-26

    • DOI

      10.1186/s41232-018-0084-7

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Human iPS cell-derived cardiac tissue sheets for functional restoration of infarcted porcine hearts.2018

    • Author(s)
      Ishigami M, Masumoto H, Ikuno T, Aoki T, Kawatou M, Minakata K, Ikeda T, Sakata R, Yamashita JK, Minatoya K.
    • Journal Title

      PLoS One.

      Volume: 13 Issue: 8 Pages: e0201650-e0201650

    • DOI

      10.1371/journal.pone.0201650

    • NAID

      120006552912

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sustained release of basic fibroblast growth factor using gelatin hydrogel improved left ventricular function through the alteration of collagen subtype in a rat chronic myocardial infarction model.2018

    • Author(s)
      Li Z, Masumoto H, Jo JI, Yamazaki K, Ikeda T, Tabata Y, Minatoya K.
    • Journal Title

      Gen Thorac Cardiovasc Surg.

      Volume: 66 Issue: 11 Pages: 641-647

    • DOI

      10.1007/s11748-018-0969-z

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A therapeutic angiogenesis of sustained release of basic fibroblast growth factor using biodegradable gelatin hydrogel sheets in a canine chronic myocardial infarction model.2018

    • Author(s)
      Kumagai M, Minakata K, Masumoto H, Yamamoto M, Yonezawa A, Ikeda T, Uehara K, Yamazaki K, Ikeda T, Matsubara K, Yokode M, Shimizu A, Tabata Y, Sakata R, Minatoya K.
    • Journal Title

      Heart Vessels

      Volume: 33 Issue: 10 Pages: 1251-1257

    • DOI

      10.1007/s00380-018-1185-6

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Impact of Cell Composition and Geometry on Human Induced Pluripotent Stem Cells-Derived Engineered Cardiac Tissue.2017

    • Author(s)
      Nakane T, Masumoto H, Tinney JP, Yuan F, Kowalski WJ, Ye F, LeBlanc AJ, Sakata R, Yamashita JK, Keller BB.
    • Journal Title

      Sci Rep.

      Volume: 7 Issue: 1 Pages: 45641-45641

    • DOI

      10.1038/srep45641

    • NAID

      120006309290

    • Related Report
      2017 Research-status Report 2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Quantification of Cardiomyocyte Alignment from Three-Dimensional (3D) Confocal Microscopy of Engineered Tissue.2017

    • Author(s)
      Kowalski WJ, Yuan F, Nakane T, Masumoto H, Dwenger M, Ye F, Tinney JP, Keller BB.
    • Journal Title

      Microsc Microanal.

      Volume: 23 Issue: 4 Pages: 826-842

    • DOI

      10.1017/s1431927617000666

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Efficient and robust differentiation of endothelial cells from human induced pluripotent stem cells via lineage control with VEGF and cyclic AMP.2017

    • Author(s)
      Ikuno T, Masumoto H, Yamamizu K, Yoshioka M, Minakata K, Ikeda T, Sakata R, Yamashita JK
    • Journal Title

      PLoS One

      Volume: 12 Issue: 3 Pages: e0173271-e0173271

    • DOI

      10.1371/journal.pone.0173271

    • NAID

      120005997909

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Untiring steps toward the maturation of human stem cell-engineered heart tissue.2017

    • Author(s)
      Masumoto H, Yamashita JK.
    • Journal Title

      Ann Transl Med

      Volume: 5 Issue: 4 Pages: 87-87

    • DOI

      10.21037/atm.2017.01.60

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Human iPS Cell-Derived Cardiac Tissue Sheets: a Platform for Cardiac Regeneration.2016

    • Author(s)
      Masumoto H, Yamashita JK.
    • Journal Title

      Curr Treat Options Cardiovasc Med.

      Volume: 18 Issue: 11 Pages: 65-65

    • DOI

      10.1007/s11936-016-0489-z

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The myocardial regenerative potential of three-dimensional engineered cardiac tissues composed of multiple human iPS cell-derived cardiovascular cell lineages.2016

    • Author(s)
      Masumoto H, Nakane T, Tinney JP, Yuan F, Ye F, Kowalski WJ, Minakata K, Sakata R, Yamashita JK, Keller BB.
    • Journal Title

      Sci Rep.

      Volume: 6 Issue: 1 Pages: 29933-29933

    • DOI

      10.1038/srep29933

    • NAID

      120005829361

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] 同種 iPS 細胞を用いた心不全治療を目指して:これからの心不全治療における iPS 細胞を用いた再生医療の役割2019

    • Author(s)
      升本英利
    • Organizer
      第18回再生医療学会総会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 心臓再生医療用のヒトiPS細胞由来心血管系細胞多層体の開発2018

    • Author(s)
      升本 英利,中根 武一郎,平尾 慎吾,瀧本 真也,李 子澎,金光 ひでお,植山 浩二,山﨑 和裕,池田 義,田畑 泰彦,山下 潤,湊谷 謙司
    • Organizer
      第118回日本外科学会定期学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ミニブタ心筋梗塞モデルに対するヒトiPS細胞由来積層化心臓組織シート移植による心機能改善効果の検討2018

    • Author(s)
      平尾 慎吾,升本 英利,西尾 博臣,川東 正英,金光 ひでお,植山 浩二,山﨑 和裕,池田 義,田畑 泰彦,山下 潤,湊谷 謙司
    • Organizer
      第118回日本外科学会定期学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] マウス下肢虚血モデルにおけるゼラチンスポンジを用いたiPS細胞由来血管構成細胞移植による血流改善および血管再生効果の検討2018

    • Author(s)
      津丸 真一,升本 英利,川東 正英,幾野 毅,金光 ひでお,植山 浩二,山﨑 和裕,池田 義,湊谷 謙司
    • Organizer
      第46回日本血管外科学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Human iPSC-derived cardiac tissue transplantation to a rat unloaded ischemic heart model2018

    • Author(s)
      Heima D, Masumoto H, Kawatou M, Osada H, Takeda M, Ikeda T, Tabata Y, Minatoya K, Yamashita J.K.
    • Organizer
      第2回日本循環器学会基礎研究フォーラム
    • Related Report
      2018 Annual Research Report
  • [Presentation] ヒトiPS細胞を用いた致死性心室性不整脈再現3次元心臓組織モデルの開発2018

    • Author(s)
      川東 正英,升本 英利,金光 ひでお,山﨑 和裕,池田 義,湊谷 謙司
    • Organizer
      第71回日本胸部外科学会定期学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 左室補助装置下の虚血性心疾患におけるヒトiPS細胞由来心臓組織移植の効果について:ラット異所性移植モデルを用いた検討2018

    • Author(s)
      平間 大介,升本 英利,川東 正英,金光 ひでお,山﨑 和裕,池田 義,湊谷 謙司
    • Organizer
      第71回日本胸部外科学会定期学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Updates for Cardiovascular Regenerative Medicine Based on Biomaterials and Beyond.2018

    • Author(s)
      Masumoto H.
    • Organizer
      第5回国際組織工学・再生医療学会世界会議
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Torsade de Pointes arrhythmia model in vitro with 3D human iPS cell-engineered heart tissue2018

    • Author(s)
      Kawatou M, Masumoto H, Ashihara T, Yamashita JK.
    • Organizer
      第5回国際組織工学・再生医療学会世界会議
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Human iPS Cell-Derived Cardiac Tissue Transplantation to a Rat Unloaded Ischemic Heart Model Mimicking Left Ventricular Assist Device Implantation2018

    • Author(s)
      Heima D, Masumoto H, Kawatou M, Osada H, Ikeda T, Tabata Y, Minatoya K, Yamashita J.K.
    • Organizer
      AHA (American Heart Association) Scientific Sessions 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 多能性幹細胞由来バイオエンジニアリング心臓組織の外科的移植による心筋再生研究2017

    • Author(s)
      升本 英利,坂田 隆造,湊谷 謙司
    • Organizer
      第47回日本心臓血管外科学会学術総会
    • Place of Presentation
      東京都
    • Year and Date
      2017-02-27
    • Related Report
      2016 Research-status Report
  • [Presentation] ヒトiPS細胞由来心臓構成細胞を用いた再生医療用の三次元人工心筋組織の開発2017

    • Author(s)
      升本 英利,中根 武一郎,南方 謙二,池田 義,坂田 隆造,湊谷 謙司,山下 潤,Bradley B.Keller.
    • Organizer
      第117回日本外科学会定期学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] Human iPS Cell-deriverd Cardiac Tissue(HiCT) for cardiac regenerative therapy2017

    • Author(s)
      Masumoto H.
    • Organizer
      European Society for Cardiology Congress 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Bioengineered cardiac cell sheets2016

    • Author(s)
      Masumoto H
    • Organizer
      HA American Heart Association 2016
    • Place of Presentation
      New Orleans, USA
    • Year and Date
      2016-11-12
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] A technology for cardiac regeneration using human iPS cell-derived cardiac tissue including multiple cardiovascular lineages2016

    • Author(s)
      Masumoto H, Yamamizu K, Ikuno T, Takakubo H, Minakata K, Ikeda T, Tabata Y, Yamashita J.K.
    • Organizer
      AHA American Heart Association 2016
    • Place of Presentation
      New Orleans, USA
    • Year and Date
      2016-11-12
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] ヒトiPS細胞由来心筋細胞および血管構成細胞を含む三次元人工心筋組織による心筋再生についての検討2016

    • Author(s)
      升本 英利,中根 武一郎,南方 謙二,池田 義,坂田 隆造
    • Organizer
      第69回日本胸部外科学会定期学術集会
    • Place of Presentation
      岡山市
    • Year and Date
      2016-09-28
    • Related Report
      2016 Research-status Report
  • [Presentation] Implantation of human iPS cell-derived engineered cardiac tissues including cardiomyocytes and multiple vascular lineages ameliorates cardiac dysfunction after myocardial infarction in a rat model2016

    • Author(s)
      Masumoto H, Nakane T, J P.Tinney, F Yuan, W J.Kowalski, Minakata K, Sakata R.
    • Organizer
      European Society of Cardiology (ESC) Congress 2016
    • Place of Presentation
      Rome, Italy
    • Year and Date
      2016-08-26
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Therapeutic potential of human iPS cell-derived engineered cardiac tissue including cardiomyocytes and multiple vascular lineages for myocardial infarction.2016

    • Author(s)
      Masumoto H, Nakane T, J P.Tinney, F Yuan, F Ye, W J.Kowalski, Minakata K, Sakata R, Yamashita J K, B B.Keller.
    • Organizer
      International Society for Stem Cell Research(ISSCR) 2016
    • Place of Presentation
      San Francisco, USA
    • Year and Date
      2016-06-22
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] ヒトiPS細胞由来心臓構成細胞を含む三次元人工心筋組織移植による心筋再生についての検討2016

    • Author(s)
      升本 英利,中根 武一郎,Joseph Tinney,南方 謙二,坂田 隆造,山下 潤,Bradley Keller.
    • Organizer
      第37回日本炎症・再生医学会
    • Place of Presentation
      京都市
    • Year and Date
      2016-06-16
    • Related Report
      2016 Research-status Report
  • [Presentation] Generation of 3-dimensional cardiac tissue with human iPS cells and tissue engineering2016

    • Author(s)
      Masumoto H
    • Organizer
      The 9th Pan Pacific Symposium on Stem Cells and Cancer Research (PPSSC)
    • Place of Presentation
      Taichung, Taiwan
    • Year and Date
      2016-05-14
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Book] Stem Cells in Clinical Practice and Tissue Engineering2018

    • Author(s)
      Nakane, T, Masumoto H, Keller BB.
    • Total Pages
      333
    • Publisher
      InTech Open
    • ISBN
      9781789230116
    • Related Report
      2018 Annual Research Report 2017 Research-status Report
  • [Remarks] 京都大学 心臓血管外科

    • URL

      http://kyoto-cvs.jp/

    • Related Report
      2018 Annual Research Report

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Published: 2016-04-21   Modified: 2020-03-30  

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