Study of drug discovery using cardiomyocytes derived from iPS cells in cardiovascular diseases

• Project/Area Number: 15H02558
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Cardiovascular surgery
• Research Institution: Osaka University
• Principal Investigator: Sawa Yoshiki 大阪大学, 医学系研究科, 教授 (00243220)
• Co-Investigator(Kenkyū-buntansha): 松崎 典弥 大阪大学, 工学研究科, 准教授 (00419467) ; 宮川 繁 大阪大学, 医学系研究科, 特任教授(常勤) (70544237) ; 秦 広樹 大阪大学, 医学系研究科, 講師 (80638198) ; 福嶌 五月 国立研究開発法人国立循環器病研究センター, 病院, 医長 (80596867) ; 仲村 輝也 大阪大学, 医学系研究科, 講師 (90511626)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥41,860,000 (Direct Cost: ¥32,200,000、Indirect Cost: ¥9,660,000); Fiscal Year 2017: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000); Fiscal Year 2016: ¥13,910,000 (Direct Cost: ¥10,700,000、Indirect Cost: ¥3,210,000); Fiscal Year 2015: ¥20,410,000 (Direct Cost: ¥15,700,000、Indirect Cost: ¥4,710,000)
• Keywords: iPS細胞 / 創薬スクリーニング / iPS由来心筋細胞 / 三次元組織 / 心毒性評価 / 心臓線維化モデル / 薬剤スクリーニングシステム / 三次元心筋組織 / 創薬 / 再生医療 / 疾患得的iPS細胞 / 三次元組織化

Outline of Final Research Achievements

In vitro drug screening model is a critical step in drug discovery for clinical use. We developed the three-dimensional cardiac tissues using cardiomyocytes derived from human induced pluripotent stem cells for evaluating cardiotoxicity. The three-dimensional cardiac tissues exhibited cardiotoxicity induced by the known drugs.　This model have great potential for in vitro drug screening with possible superiority to two-dimensional cardiomyocytes, suggesting that three-dimensional cardiac tissues may play crucial roles for drug repositioning or development in new cardiovascular agents.
In addition, we developed the cardiac fibrosis model using cardiomyocytes derived from human induced pluripotent stem cells. The cardiac fibrosis model showed great responses to fibrosis stimulus similar to human, indicating its usefulness for drug screening system for drug anti fibrotic drugs.

Research Products

• [Journal Article] Development of in Vitro Drug-Induced Cardiotoxicity Assay by Using Three-Dimensional Cardiac Tissues (2018)
  • Author(s): Takeda M, Miyagawa S, Fukushima S, Saito A, Ito E, Harada A, Matsuura R, Iseoka H, Sougawa N, Mochizuki-Oda N, Matsusaki M, Akashi M, Sawa Y
  • Journal Title: Tissue Eng Part C Methods Volume: 24(1) Issue: 1 Pages: 56-67
  • DOI: 10.1089/ten.tec.2017.0247
  • Peer Reviewed / Open Access
• [Journal Article] Construction of mES Derived 3D-Pacemaker Tissues by Layer-by-Layer Nanofilm Coating (2016)
  • Author(s): Y. Amano, T. Igarashi, A. Nishiguchi, M. Matsusaki, Y. Saito, K. Nakamura, H. Ito, M. Akashi
  • Journal Title: ChemNanoMat, Volume: 24 Feb Issue: 5 Pages: 1-1
  • DOI: 10.1002/cnma.201600031
  • Peer Reviewed
• [Journal Article] Development of Vascularized iPSC Derived 3D-Cardiac Myoblast Tissues by Filtration Layer-by-Layer Technique and Their Application for Pharmaceutical Assays (2016)
  • Author(s): Yuto Amano, Akihiro Nishiguchi, Michiya Matsusaki, Hiroko Iseoka, Shigeru Miyagawa, Yoshiki Sawa, Manabu Seo, Takashi Yamaguchi, Mitsuru Akashi,
  • Journal Title: Acta Biomater Volume: 33 Pages: 110-121
  • DOI: 10.1016/j.actbio.2016.01.033
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Control of Vascular Network Location in Millimeter-sized 3D-Tissues by Micrometer-sized Collagen Coated Cells (2016)
  • Author(s): C. Y. Liu, M. Matsusaki, M. Akashi
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 472 Issue: 1 Pages: 131-136
  • DOI: 10.1016/j.bbrc.2016.02.080
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Three-dimensional Tissue Models Constructed by Cells with Nanometer- or Micrometer-Sized Films on Their Surfaces (2016)
  • Author(s): Chun-Yen Liu, Michiya Matsusaki, Mitsuru Akashi,
  • Journal Title: Chem. Rec. Volume: in press Issue: 2 Pages: 1-1
  • DOI: 10.1002/tcr.201500272
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] Building a New Drug Screening System for Evaluating Cardiotoxicity by Three-dimensional Micro Cardiac Tip Derived from Induced Pluripotent Stem cells (2018)
  • Author(s): Maki Takeda, Shigeru Miyagawa, Emiko Ito, Akima Harada, Noriko Mochizuki-Oda, Yoshiki Sawa
  • Organizer: 第82回日本循環器学会
• [Presentation] 創薬スクリーニングを目的としたヒトiPS細胞由来3次元心筋組織の作製 (2018)
  • Author(s): 武田真季 宮川繁 伊東絵望子 原田明希摩 小田-望月紀子 明石満 澤芳樹
  • Organizer: 第17回日本再生医療学会学術集会
• [Presentation] 毛細血管構造を有するヒトiPS細胞由来三次元組織体チップの創製と薬剤毒性試験への応用 (2016)
  • Author(s): 松崎典弥、天野雄斗、西口昭広、宮川繁、澤芳樹、明石満
  • Organizer: 第15回日本再生医療学会総会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2016-03-17
• [Presentation] ヒトiPS細胞由来3次元心筋組織を用いた薬剤安全性スクリーニングシステムの検討 (2016)
  • Author(s): 武田真季、宮川繁、福嶌五月、齋藤充弘、伊東絵望子、原田明希摩、松浦良平、小田-望月紀子、松崎典弥、明石満、澤芳樹
  • Organizer: 第15回日本再生医療学会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2016-03-17
• [Presentation] Development of Vascularized iPSC Derived 3D-Cardiac Myoblast Tissues by Filtration Layer-by-Layer Technique (2015)
  • Author(s): Y. Amano, A. Nishiguchi, M. Matsusaki, S. Miyagawa, Y. Sawa, M. Akashi
  • Organizer: Pacifichem 2015
  • Place of Presentation: Honolulu, USA
  • Year and Date: 2015-12-15
  • Int'l Joint Research
• [Presentation] 細胞コート法によるヒトiPS細胞由来三次元心筋組織体の構築と薬剤評価への応用 (2015)
  • Author(s): 天野雄斗、西口昭広、松崎典弥、宮川繁、澤芳樹、明石満
  • Organizer: 第37回日本バイオマテリアル学会大会
  • Place of Presentation: 京都テルサ
  • Year and Date: 2015-11-09
• [Presentation] Development of In Vitro Drug-Induced Cardiotoxicity Assay by Using Three-Dimensional Cardiac Tissues Derived from Human Induced Pluripotent Stem Cells (2015)
  • Author(s): Takeda M, Miyagawa S, Fukushima S, Saito A, Ito E, Matsuura R, Harada A. Shiozaki M, Amano Y, Matstusaki M, Akasi M
  • Organizer: American Heart Association Scientific Sessions
  • Place of Presentation: Orlando, USA
  • Year and Date: 2015-11-07