Development of comprehensive cardiac regeneration strategies with human ES cells

2008 Fiscal Year Final Research Report

• Project/Area Number: 19390213
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Kyoto University
• Principal Investigator: YAMASHITA Jun Kyoto University, 再生医科学研究所, 准教授 (50335288)
• Project Period (FY): 2007 – 2008
• Keywords: ES細胞 / 心臓再生 / 心筋分化 / ペースメーカー / 前駆細胞

Research Abstract

代表者はマウスES細胞を用いて循環器系細胞を系統的に誘導できる新しい分化誘導系を開発した。本研究は、同システムを用いて、新たな心臓再生治療応用シーズを探索し、細胞・遺伝子・薬剤など新たな治療法を包括的に開拓することを目的とした。心筋細胞の自動能維持機構の解析、心筋及び心筋前駆細胞分化誘導効率を約10倍高める物質の同定、人工多能性幹細胞(iPS細胞)からの心血管分化誘導法の開発を行い、種々の心臓再生戦略のシーズ開発に成功した。

Research Products

• [Journal Article] Cyclosporin-A potently induces highly cardiogenic progenitors from embryonic stem cells (2009)
  • Author(s): Yan P, Nagasawa A, Uosaki H, Sugimoto A, Yamamizu K, Teranishi M, Matsuda H, Matsuoka S, Ikeda T, Komeda M, Sakata R, Yamashita JK
  • Journal Title: Biochem Biophys Res Commun 379 Pages: 115-120
• [Journal Article] Directed and systematic differentiation of cardiovascular cells from mouse induced pluripotent stem cells (2008)
  • Author(s): Narazaki G, Uosaki M, Teranishi M, Okita K, Kim B, Matsuoka S, Yamanaka S, Yamashita JK
  • Journal Title: Circulation(Circulation 2008, Best Paper Award in Basic Science) 118 Pages: 498-506
• [Journal Article] Evaluation of antiangiogenic activity of azumamides by the in vitro vascular organization model using mouse induced pluripotent stem (iPS) cells (2008)
  • Author(s): Nakao Y, Narazaki G, Hoshino T, Maeda S, Yoshida M, Maejima H, Yamashita JK
  • Journal Title: Bioorg Med Chem Lett 18 Pages: 2982-2984
• [Journal Article] Hyperpolarization-activated cyclic nucleotide-gated channels and T-type calcium channels confer automaticity of embryonic stem cell-derived cardiomyocytes (2007)
  • Author(s): Yanagi K, Takano M, Narazaki G, Uosaki H, Hoshino T, Ishii T, Misaki T, Yamashita JK
  • Journal Title: Stem Cells 25 Pages: 2712-2719
• [Journal Article] Pathway for differentiation of human embryonic stem cells to vascular cell components and their potential for vascular regeneration (2007)
  • Author(s): Sone M, Itoh h, Yamahara K, Yamashita JK, Yurugi-Kobayashi T, Nonoguchi A, Suzuki Y, Chao TH, Sawada N, Fukunaga Y, Miyashita K, Park K, Oyamada N, Sawada N, Taura D, Tamura N, Kondo Y, Nito S, Suemori H, Nakatsuji N, Nishikawa SI, Nakao K
  • Journal Title: Arterioscler Thromb Vasc Biol 27 Pages: 2127-2134
• [Journal Article] Differentiation of arterial, venous, and lymphatic endothelial cells from vascular progenitors (2007)
  • Author(s): Yamashita JK
  • Journal Title: Trends Cardiovasc Med 17 Pages: 59-63
• [Presentation] Systematic differentiation system of mouse induce pluripotent stem (iPS) cells to cardiovacular cells (2008)
  • Author(s): Narazaki G, Yamashita JK
  • Organizer: The 6th Korea-Japan Joint Symposium on Vascular Biology And The 16th Annual Meeting of the Japan Vascular Biology and Medicine Organization Joint Meeting
  • Place of Presentation: Kanazawa(invited)
  • Year and Date: 20081203-05
• [Presentation] Molecular mechanisms of arterial-venous specification (2008)
  • Author(s): Yamashita JK
  • Organizer: 第16回日本血管生物医学会・日韓合同血管生物シンポジウム
  • Place of Presentation: 金沢(invited)
  • Year and Date: 20081203-05
• [Presentation] Notchと beta-catenin シグナルによる新しい動脈内皮細胞分化誘導機構 (2008)
  • Author(s): 山水康平、山下潤
  • Organizer: 第15回心血管内分泌代謝学会YIA審査講演
  • Place of Presentation: 熊本
  • Year and Date: 20081128-29
• [Presentation] Converged signaling of Notch and beta-catenin induces differentiation of arterial endothelial cells from VEGFR2+ vascular progenitors (2008)
  • Author(s): Yamamizu K, Yamashita JK
  • Organizer: American Heart Association Scientific Session 2008
  • Place of Presentation: New Orleans, USA(Oral presentation)
  • Year and Date: 20081108-14
• [Presentation] ES細胞およびiPS細胞を用いた心血管分化再生研究 (2008)
  • Author(s): 山下潤
  • Organizer: 第1回臨床研究フォーラム
  • Place of Presentation: 御殿場(特別講演)
  • Year and Date: 20080808-09
• [Presentation] Cardiovascular Cell Differentiation System Using Mouse Induced Pluripotent Stem Cells (2008)
  • Author(s): Narazaki G, Teranishi M, Uosaki H, Okita K, Kim BJ, Matsuoka S, Yamanaka S, Yamashita JK
  • Organizer: 6th ISSCR Annual Meeting
  • Place of Presentation: Philadelphia, USA
  • Year and Date: 20080611-14
• [Presentation] Phosphatidylinositol 3-kinase pathway and Notch signaling coordinately induce differentiation of arterial endothelial cells from vascular progenitors (2008)
  • Author(s): Yamamizu K, Yamashita JK
  • Organizer: The 15th International Vascular Biology Meeting
  • Place of Presentation: Sydney, Australia(Oral presentation)
  • Year and Date: 20080601-05
• [Presentation] Efficient and Specific Expansion of Highly Cardiogenic Progenitors from Embryonic Stem Cells by Cyclosporin-A treatment (2008)
  • Author(s): Yan P, Otsuji T, Nagasawa A, Narazaki G, Uosaki H, Sugimoto A, Fujiwara M, Ikeda T, Nakao K, Yamanaka S, Nakatsuji N, Komeda M, Yamashita JK
  • Organizer: 第72回日本循環器学会留学生YIA審査講演
  • Place of Presentation: 福岡
  • Year and Date: 20080328-30
• [Presentation] Effective cardiac regeneration in vivo by ES cell-derived cardiac progenitors (2008)
  • Author(s): Yamashita JK
  • Organizer: Japan-Korea Cardiovascular Conference, 第72回日本循環器学会
  • Place of Presentation: 福岡(特別講演)
  • Year and Date: 20080328-30
• [Presentation] Cellular and molecular mechanisms for diversification of arterial, venous, and lymphatic endothelial cells (2008)
  • Author(s): Yamashita JK
  • Organizer: THE U.S.-JAPAN COOPERATIVE CANCER RESEARCH PROGRAM WORKSHOP 2008
  • Place of Presentation: Kyoto(invited)
  • Year and Date: 20080319-21
• [Presentation] ES細胞及びiPS細胞を用いた心血管分化再生研究 (2008)
  • Author(s): 山下潤
  • Organizer: 熊本Science Frontier研究会
  • Place of Presentation: 熊本(特別講演)
  • Year and Date: 2008-12-10
• [Presentation] ES細胞及びiPS細胞からの心血管分化 (2008)
  • Author(s): 山下潤
  • Organizer: BMB2008シンポジウム:1S1 多能性幹細胞を規定する因子群-臨床応用を見据えて-
  • Place of Presentation: 神戸(特別講演)
  • Year and Date: 2008-12-09
• [Presentation] Research for vascular development and regeneration using ES and iPS cells (2008)
  • Author(s): Yamashita JK
  • Organizer: The 24th Kumamoto Medical Bioscience Symposium "Frontiers of Vascular Medical Science and Innovative Therapy"
  • Place of Presentation: Kumamoto(invited)
  • Year and Date: 2008-11-27
• [Presentation] Specific Expansion of Cardiac Progenitors and Cardiomyocytes from ES and iPS Cells (2008)
  • Author(s): Yamashita JK
  • Organizer: Specific Expansion of Cardiac Progenitors and Cardiomyocytes from ES and iPS Cells
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2008-11-20
• [Presentation] 幹細胞と再生医学 -心臓や血管は再生できるか- (2008)
  • Author(s): 山下潤
  • Organizer: 京都南ロータリークラブ講演会
  • Place of Presentation: 京都(特別講演)
  • Year and Date: 2008-10-16
• [Presentation] ES細胞及びiPS細胞を用いた心血管分化再生研究 (2008)
  • Author(s): 山下潤
  • Organizer: 佐賀・生活習慣病フォーラム2008
  • Place of Presentation: 佐賀(特別講演)
  • Year and Date: 2008-08-02
• [Presentation] ES細胞及びiPS細胞を用いた心血管分化再生研究 (2008)
  • Author(s): 山下潤
  • Organizer: 心血管再生先端治療フォーラム
  • Place of Presentation: 東京(特別講演)
  • Year and Date: 2008-07-05
• [Presentation] ES細胞及びiPS細胞を用いた心血管分化再生研究 (2008)
  • Author(s): 山下潤
  • Organizer: 山口免疫懇話会
  • Place of Presentation: 山口(特別講演)
  • Year and Date: 2008-03-05
• [Presentation] ES細胞を用いた新しい構成的アプローチによる血管分化多様化機構の解析と再構成 (2007)
  • Author(s): 山下潤
  • Organizer: 第30回日本分子生物学会ワークショップ「血管リンパ管研究の新展開」
  • Place of Presentation: 横浜(オーガナイザー)
  • Year and Date: 2007-12-14
• [Presentation] ES細胞を用いた構成的アプローチによる血管分化多様化機構の解析 (2007)
  • Author(s): 山下潤
  • Organizer: 日本血栓止血学会シンポジウム
  • Place of Presentation: 三重(特別講演)
  • Year and Date: 2007-11-16
• [Presentation] Prospective identification of cardiac progenitors (2007)
  • Author(s): Yamashita JK
  • Organizer: 4th Annual Symposium of the American Heart Association Council on Basic Cardiovascular Sciences -Cardiovascular Repair and Regeneration
  • Place of Presentation: Keystone, USA(Invited)
  • Year and Date: 2007-07-30
• [Book] 幹細胞の分化誘導と応用-ES細胞・iPS細胞・体性幹細胞研究最前線- (2009)
  • Author(s): 山下潤
  • Total Pages: 253-261
  • Publisher: ES細胞、iPS細胞を用いた血管再生医療技術
• [Book] EW. Recent Advances in Thrombosis and Hemostasis 2008 (2008)
  • Author(s): Yamashita JK
  • Total Pages: 363-373
  • Publisher: A linkage in the developmental pathway of vascular and hematopoietic cells.In Tanaka K, Davie EW
• [Patent(Industrial Property Rights)] Efficient production and use of highly cardiogenic progenitors and cardiomyocytes from embryonic and induced pluripotent stem cells (2008)
  • Inventor(s): 山下潤、顔培実
  • Industrial Property Rights Holder: 京都大学
  • Industrial Property Number: PCT/JP2008/066033
  • Filing Date: 2008-08-29