Discovery and characterization of ES/iPSCs-cardiac differentiation promoting molecules by using chemical screening system

• Project/Area Number: 23710269
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Chemical biology
• Research Institution: Kyoto University
• Principal Investigator: MINAMI Itsunari 京都大学, 物質-細胞統合システム拠点, 助教 (40362537)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: iPS細胞 / 心筋分化 / ケミカルスクリーニング / 低分子化合物 / 臨床グレード / ヒトES/iPS細胞 / 再生医療 / ケミカルバイオロジー

Research Abstract

I discovered a novel small molecule (KY02111) by the chemical screening system using ES cells. This molecule promotes iPS-cardiac differentiation strongly and robustly. By using this molecule, I developed a new cardiac differentiation method that has many advantages for clinical application because of high efficiency, no xeno-contamination and low cost. In addition, this method can create mature cardiac cellsfrom iPSCs comparing with other studies. This study was published by Cell Reports (a sister journal of Cell) and selected for ‘Best of Cell Reports’ of 2012. Moreover, we made cardiac sheets by using my method, and for the first time, we established a heart disease model that is the spiral wave propagation in an arrhythmia after myocardial infarction.

Research Products

• [Journal Article] Development of a reentrant arrhythmia model in human pluripotent stem cell-derivpd cardiac cell sheets (2013)
  • Author(s): Kadota S, et al.
  • Journal Title: European Heart Journal Volume: VOL.34 Issue: 15 Pages: 1147-1156
  • DOI: 10.1093/eurheartj/ehs418
  • Peer Reviewed
• [Journal Article] A small molecule that promotes cardiac differentiation of human pluripotent stem cells under defined, cytokine- and xeno-free conditions (2012)
  • Author(s): Minami I, Yamada K, Otsuji TG, Yamamoto T, Shen Y, Otsuka S, Kadota S, Morone N, Barve M, Asai Y, Heuser TT, Heuser JE, Uesugi M, Aiba K, Nakatsuji N
  • Journal Title: Cell Reports
  • Peer Reviewed
• [Journal Article] A small molecule that promotes cardiac differentiation of human pluripotent stem cells under defined, cytokine- and xeno-free conditions (2012)
  • Author(s): Minami I, Yamada K, Otsuji TG, Yamamoto T, Shen Y, Otsuka S, Kadota S, Morone N, Barve M, Asai Y, Tenkova-Heuser T, Heuser JE, Uesugi M, Aiba K, Nakatsuji N
  • Journal Title: Cell Rep Volume: 2(5) Issue: 5 Pages: 1448-60
  • DOI: 10.1016/j.celrep.2012.09.015
  • Peer Reviewed
• [Presentation] NOVEL SMALL MOLECULES FACILITATE HIGH EFFICIENT CARDIAC DIFFERENTIATION FROM ES AND IPS CELLS (2011)
  • Author(s): Itsunari Minami
  • Organizer: ISSCR 9th Annual Meeting
  • Place of Presentation: Canada, Toronto
• [Remarks] ヒトES/iPS細胞から臨床応用に適した心筋分化誘導法を開発
  • URL: http://www.icems.kyoto-u.ac.jp/j/pr/2012/10/26-nr.html
• [Remarks] ヒトES/iPS細胞から作った心筋細胞シートで不整脈モデルを開発
  • URL: http://www.icems.kyoto-u.ac.jp/j/pr/2012/12/01-nr.html
• [Remarks] ヒトES/iPS細胞から臨床応用に適した心筋分化誘導法を開発
  • URL: http://www.icems.kyoto-u.ac.jp/j/pr/2012/10/26-nr.html
• [Remarks] ヒトES/iPS細胞から作った心筋細胞シートで不整脈モデルを開発
  • URL: http://www.icems.kyoto-u.ac.jp/j/pr/2012/12/01-nr.html
• [Patent(Industrial Property Rights)] 多能性幹細胞の心筋分化誘導法 (2013)
  • Inventor(s): 中辻憲夫、南一成、上杉志成、饗庭一博
  • Industrial Property Rights Holder: 中辻憲夫、南一成、上杉志成、饗庭一博
  • Filing Date: 2013-01-25
  • Overseas
• [Patent(Industrial Property Rights)] 多能性幹細胞の心筋分化促進剤 (2011)
  • Inventor(s): 中辻憲夫、南一成、上杉志成、山田耕平
  • Industrial Property Rights Holder: 中辻憲夫、南一成、上杉志成、山田耕平
  • Filing Date: 2011-08-24
  • Overseas