Innovation of the novel cardiac regeneration therapy using gene introduction-mediated cell conversion into cardiac progenitor cells.

• Project/Area Number: 21890117
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Circulatory organs internal medicine
• Research Institution: Kyoto University
• Principal Investigator: KAWAMURA Teruhisa Kyoto University, 生命科学系キャリアバス形成ユニット, 助教 (90393199)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000); Fiscal Year 2010: ¥1,235,000 (Direct Cost: ¥950,000、Indirect Cost: ¥285,000); Fiscal Year 2009: ¥1,365,000 (Direct Cost: ¥1,050,000、Indirect Cost: ¥315,000)
• Keywords: 分子心臓病態学 / 再生医学 / 幹細胞生物学 / 体細胞初期化

Research Abstract

Recent technologies to reprogram somatic cells into induced pluripotent stem (iPS) cells have been expected as a powerful tool of regeneration therapy for end-staged heart failure. However, duration of iPS cell derivation and the risk of tumorigenesis including teratoma after cell implantation as well as limited efficiency for cardiac differentiation are considered as great barriers against the clinical application of this powerful approach. To overcome these problems, by modifying the reprograming process, here we show the novel alternative strategy which enables us to create cardiac myocytes directly from fibroblasts rapidly and efficiently with a low risk of tumorigenesis. In addition, we established the mouse experimental model to evaluate the effect of this strategy as an innovative cardiac regeneration therapy.

Research Products

• [Journal Article] MicroRNA-27a regulates beta cardiac myosin heavy chain gene expression by targeting thyroid hormone receptor betal in neonatal rat ventricular myocytes. (2011)
  • Author(s): Nishi H, Ono K, Horie T, Nagao K, Kinoshita M, Kuwabara Y, Watanabe S, Takaya T, Tamaki Y, Takanabe-Mori R, Wada H, Hasegawa K, Iwanaga Y, Kawamura T, Kita T, Kimura T.
  • Journal Title: Mol Cell Biol. 31 Pages: 744-755
  • Peer Reviewed
• [Journal Article] Cyclin-dependent kinase 9 forms a complex with GATA4 and is involved in the differentiation of mouse ES cells into cardiomyocytes. (2011)
  • Author(s): Kaichi S, Takaya T, Morimoto T, Sunagawa Y, Kawamura T, Ono K, Shimatsu A, Baba S, Heike T, Nakahata T, Hasegawa K.
  • Journal Title: J Cell Physiol. 226 Pages: 248-254
  • Peer Reviewed
• [Journal Article] MicroRNA-27a regulates beta cardiac myosin heavy chain gene expression by targeting thyroid hormone receptor beta1, in neonatal rat ventricular myocytes. (2011)
  • Author(s): Nishi H, Ono K, Horie T, Nagao K, Kinoshita M, Kuwabara Y, Watanabe S, Takaya T, Tamaki Y, Takanabe-Mori R, Wada H, Hasegawa K, Iwanaga Y, Kawamura T, Kita T, Kimura T.
  • Journal Title: Mol Cell Biol. Volume: 31 Pages: 744-755
  • NAID: 120002871162
  • Peer Reviewed
• [Journal Article] Cyclin-dependent kinase 9 forms a complex with GATA4 and is involved in the differentiation of mouse ES cells into cardiomyocytes. (2011)
  • Author(s): Kaichi S, Takaya T, Morimoto T, Sunagawa Y, Kawamura T, Ono K, Shimatsu A, Baba S, Heike T, Nakahata T, Hasegawa K.
  • Journal Title: J Cell Physiol. Volume: 226 Pages: 248-254
  • Peer Reviewed
• [Journal Article] Cell line-dependent differentiation of induced pluripotent stem cells into cardiomyocytes in mice. (2010)
  • Author(s): Kaichi S, Hasegawa K, Takaya T, Yokoo N, Mima T, Kawamura T, Morimoto T, Ono K, Baba S, Doi H, Yamanaka S, Nakahata T, Heike T.
  • Journal Title: Cardiovasc Res. 88 Pages: 314-323
  • Peer Reviewed
• [Journal Article] Human and mouse adipose-derived cells support feeder independent induction of pluripotent stem cells. (2010)
  • Author(s): Sugii S, Kida Y, Kawamura T, Suzuki J, Vassena R, Yin YQ, Lutz MK, Berggren WT, Izpisua-Belmonte JC, Evans RM.
  • Journal Title: Proc Natl Acad Sci USA. 107 Pages: 3558-3563
  • Peer Reviewed
• [Journal Article] Cell line-dependent differentiation of induced pluripotent stem cells into cardiomyocytes in mice. (2010)
  • Author(s): Kaichi S, Hasegawa K, Takaya T, Yokoo N, Mima T, Kawamura T, Morimoto T, Ono K, Baba S, Doi H, Yamanaka S, Nakahata T, Heike T.
  • Journal Title: Cardiovasc Res. Volume: 88 Pages: 314-323
  • Peer Reviewed
• [Journal Article] Human and mouse adipose-derived cells support feeder independent induction of pluripotent stem cells. (2010)
  • Author(s): Sugii S, Kida Y, Kawamura T, et al.
  • Journal Title: Proc Natl Acad Sci USA. 107 Pages: 3558-3563
  • Peer Reviewed
• [Journal Article] Linking the p53 tumour suppressor pathway to somatic cell reprogramming. (2009)
  • Author(s): Kawamura T, Suzuki J, Wang YV, Menendez S, Batlle Morera L, Raya A, Wahl GM, Izpisua-Belmonte JC.
  • Journal Title: Nature. 460 Pages: 1140-1144
  • Peer Reviewed
• [Journal Article] MicroRNA-1 and MicroRNA-133 in spontaneous myocardial differentiation of mouse embryonic stem cells. (2009)
  • Author(s): Takaya T, Ono K, Kawamura T, Takanabe R, Kaichi S, Morimoto T, Wada H, Kita T, Shimatsu A, Hasegawa K.
  • Journal Title: Circ J. 73 Pages: 1492-1497
  • NAID: 10025933876
  • Peer Reviewed
• [Journal Article] Linking the p53 tumour suppressor pathway to somatic cell reprogramming. (2009)
  • Author(s): Kawamura T, 筆頭著者, et al.
  • Journal Title: Nature 460 Pages: 1140-1144
  • Peer Reviewed
• [Journal Article] MicroRNA-1 and MicroRNA-133 in spontaneous myocardial differentiation of mouse embryonic stem cells. (2009)
  • Author(s): Takaya T, Ono K, Kawamura T, et al.
  • Journal Title: Circ J. 73 Pages: 1492-1497
  • NAID: 10025933876
  • Peer Reviewed
• [Presentation] iPS細胞誘導過程における細胞運命決定機構を探る (2010)
  • Author(s): 川村晃久
  • Organizer: CKDと心血管イベントExpert Meeting V
  • Place of Presentation: 東京(招待講演)
  • Year and Date: 2010-07-10
• [Presentation] Efficient creation of induced pluripotent stem cells for myocardial regeneration therapy. (2010)
  • Author(s): Sogo T, Takaya T, Shigeno A, Kojima Y, Hasegawa K, Kawamura T.
  • Organizer: 2010 World Heart Federation
  • Place of Presentation: Beijing, China
  • Year and Date: 2010-06-19
• [Presentation] Efficient creation of induced pluripotent stem cells for myocardial regeneration therapy. (2010)
  • Author(s): Sogo T, Takaya T, Shigeno A, Kojima Y, Hasegawa K, Kawamura T.
  • Organizer: World Heart Federation
  • Place of Presentation: Beijing, China
  • Year and Date: 2010-06-19
• [Presentation] Role of Wnt signaling in cardiac differentiation from mouse embryonic stem cells and induced pluripotent stem cells. (2010)
  • Author(s): Shigeno A, Sogo T, Takaya T, Kojima Y, Hasegawa K, Kawamura T.
  • Organizer: 2010 World Heart Federation
  • Place of Presentation: Beijing, China
  • Year and Date: 2010-06-18
• [Presentation] Role of Wnt signaling in cardiac differentiation from mouse embryonic stem cells and induced pluripotent stem cells. (2010)
  • Author(s): Shigeno A, Sogo T, Takaya T, Kojima Y, Hasegawa K, Kawamura T.
  • Organizer: World Heart Federation
  • Place of Presentation: Beijing, China
  • Year and Date: 2010-06-18
• [Presentation] p53 tumor suppressor pathway as a novel checkpoint during somatic cell reprogramming. (2010)
  • Author(s): Kawamura T, Suzuki J.
  • Organizer: 第9回再生医療学会
  • Place of Presentation: 広島(招待シンポジスト)
  • Year and Date: 2010-03-18
• [Presentation] p53 tumor suppressor pathway as a novel checkpoint during somatic cell reprogramming. (2010)
  • Author(s): Kawamura T, Suzuki J
  • Organizer: 第9回再生医療学会(招待シンポジウト)
  • Place of Presentation: 広島
  • Year and Date: 2010-03-18
• [Presentation] Links between p53 tumor suppressor pathway and somatic cell reprogramming. (2009)
  • Author(s): Kawamura T, Jotaro Suzuki J, Wahl GM, Izpisua-Belmonte JC.
  • Organizer: 第32回分子生物学会年会(ワークショップ)
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-09
• [Presentation] Links between p53 tumor suppressor pathway and somatic cell reprogramming. (2009)
  • Author(s): Kawamura T, Suzuki J, Wahl GM, Izpisua-Belmonte JC.
  • Organizer: 第32回分子生物学会年会(ワークショップ口頭発表)
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-09
• [Presentation] The p53 pathway as a guardian against reprogramming. (2009)
  • Author(s): 川村晃久
  • Organizer: The 5th China-Japan Cardiovascular Forum
  • Place of Presentation: Beijing, China(招待講演)
  • Year and Date: 2009-10-12
• [Presentation] The p53 pathway as a guardian against reprogramming (2009)
  • Author(s): Kawamura T.
  • Organizer: The 5^<th> China-Japan Cardiovascular Forum(招待講演)
  • Place of Presentation: 北京(中国)
  • Year and Date: 2009-10-12
• [Book] アンチ・エイジング医学-日本抗加齢医学会雑誌 (2011)
  • Author(s): 川村晃久、十河孝浩
  • Total Pages: 6
  • Publisher: メディカルレビュー社
• [Remarks] ホームページ等
  • URL: http://www.cp.kyoto-u.ac.jp/Kawamura/KawamuraIndex.html
• [Remarks] 研究室ホームページ
• [Remarks] 研究室ホームページ
  • URL: http://www.cp.kyoto-u.ac.jp/Kawamura/KawamuraIndex.html