Novel method of cardiac reprogramming with the regulator of cardiac progenitor cells.

• Project/Area Number: 17K16024
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular medicine
• Research Institution: University of Tsukuba (2018-2019); Keio University (2017)
• Principal Investigator: Isomi Mari 筑波大学, 医学医療系, 研究員 (60748490)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 心臓再生 / 幹細胞 / 心臓前駆細胞 / 分子心臓学

Outline of Final Research Achievements

There are some problems in the method to induce pluripotent stem cells into cardiomyocytes using cytokines and small molecules. Here we show Tbx6 induces Cardiac progenitor cells (CPCs) from pluripotent stem cells (PSCs) and determines cardiovascular lineage specification via its temporal expression. This method is possible to solve the above problems. Moreover, we elucidated the molecular mechanisms of CPC differentiation.

Academic Significance and Societal Importance of the Research Achievements

現在広く用いられている心筋誘導法は複数のサイトカインや化合物を使用するが、高コスト、工程が煩雑、分化メカニズムも不明などの課題があった。本研究で開発した方法はTbx6のみの発現で心臓前駆細胞を選択的に誘導することが可能なため、従来法と比較して安価かつ簡便な方法である。これらのことから今後の再生医療に大きく貢献することが予想される。

Research Products

• [Journal Article] Progress and Challenge of Cardiac Regeneration to Treat Heart Failure (2019)
  • Author(s): Isomi Mari、Sadahiro Taketaro、Ieda Masaki
  • Journal Title: Journal of Cardiology Volume: 73 Issue: 2 Pages: 97-101
  • DOI: 10.1016/j.jjcc.2018.10.002
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Role of cyclooxygenase-2-mediated prostaglandin E2-prostaglandin E receptor 4 signaling in cardiac reprogramming (2019)
  • Author(s): Muraoka Naoto、Nara Kaori、Tamura Fumiya、Kojima Hidenori、Yamakawa Hiroyuki、Sadahiro Taketaro、Miyamoto Kazutaka、Isomi Mari、Haginiwa Sho、Tani Hidenori、Kurotsu Shota、Osakabe Rina、Torii Satoru、Shimizu Shigeomi、Okano Hideyuki、Sugimoto Yukihiko、Fukuda Keiichi、Ieda Masaki
  • Journal Title: Nature Communications Volume: 10 Issue: 1 Pages: 674-674
  • DOI: 10.1038/s41467-019-08626-y
  • NAID: 120007128245
  • Peer Reviewed / Open Access
• [Journal Article] Tbx6 Induces Nascent Mesoderm from Pluripotent Stem Cells and Temporally Controls Cardiac versus Somite Lineage Diversification. (2018)
  • Author(s): Sadahiro T, Isomi M, Muraoka N, Kojima H, Haginiwa S, Kurotsu S, Tamura F, Tani H, Tohyama S, Fujita J, Miyoshi H, Kawamura Y, Goshima N, Iwasaki YW, Murano K, Saito K, Oda M, Andersen P, Kwon C, Uosaki H, Nishizono H, Fukuda K, Ieda M
  • Journal Title: Cell stem cell Volume: 23(3) Issue: 3 Pages: 382-395
  • DOI: 10.1016/j.stem.2018.07.001
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 新規心臓前駆細胞誘導因子によるヒトES/iPSからの簡便な心筋 (2017)
  • Author(s): 礒見まり
  • Organizer: Molecular Cardiovascular Metabolic Conference