Development of comprehensive cardiac regeneration strategies with human ES cells

• 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
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥18,330,000 (Direct Cost: ¥14,100,000、Indirect Cost: ¥4,230,000); Fiscal Year 2008: ¥8,710,000 (Direct Cost: ¥6,700,000、Indirect Cost: ¥2,010,000); Fiscal Year 2007: ¥9,620,000 (Direct Cost: ¥7,400,000、Indirect Cost: ¥2,220,000)
• Keywords: ES細胞 / 心臓再生 / 心筋分化 / ペースメーカー / 前駆細胞 / 心筋前駆細胞 / 心筋再生 / iPS細胞 / サイクロスポリンA / 心筋 / イオンチャネル

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] Cyclosporin-A potenly induces highly cardiogenic progenitors from embryonic stem cells. (2009)
  • Author(s): Yan P. Sagasawa A, Uosaki H, Sugimoto A, Yamaniizu K, Teranishi M. Matsuda H. Malsuoka S, Ikeda T, Komeda M, Sakala R, Yamashita JK*.
  • Journal Title: Biochem Biophys Res Commun 379 Pages: 115-120
  • Peer Reviewed
• [Journal Article] Creations of biological pacemaker (2009)
  • Author(s): Narazaki G, Yamashita JK.
  • Journal Title: Inflammation and Regeneration. 29 Pages: 123-127
• [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] 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. Yamaiiaka S, Yamashita JK*
  • Journal Title: Circulation 118 Pages: 498-506
  • Peer Reviewed
• [Journal Article] Evaluation of antiangiogenic activity of azumaiides by the in vitro vascular organization model using mouse induced pluripotent stem (iPS) cells. (2008)
  • Author(s): Nakao Y*, Xarazaki G, Hoshino T, Maeda S, Yoshida M. Maejima H, Yamashita JK*
  • Journal Title: Bioorg Med Chem Lett 18 Pages: 2982-2984
  • Peer Reviewed
• [Journal Article] Augmentation of neovasculanzaiton in hindilimb ischemia by combined transplantation of human embryonic stem cells-derived endothelial and mural cells. (2008)
  • Author(s): Yamahra K, Sone M, Itoh H. Yamashlta JK. Yurugi-Kobayashi T, Homma K, Chao TH, Miyashita K, Park K, Oyantada X, Sawada X, Taura D. Tamura X, Xakao K.
  • Journal Title: PLoS One 3
  • Peer Reviewed
• [Journal Article] Identification of adherens junction-associated GTPase activating proteins by the fluorescence localization based expression cloning. (2008)
  • Author(s): Mastuda M, Kobayashi Y. Masuda S. Adachi M. Watanabe T. Yamashita JK Nishi E, Tsukita S, Furuse M.
  • Journal Title: Exp Cell Res 314 Pages: 939-949
  • Peer Reviewed
• [Journal Article] Cyclic strain induces mouse embryonic stem cell differentiation into vascular smooth muscle cells bt activating PDGF receptor {beta}. (2008)
  • Author(s): Shimizu N, Yamaoto K, Obi S. Kumagaya S, Masumura T. Shimano Y. Naruse K. Yamashita JK. Igarashi T. Ando J.
  • Journal Title: J Appl Physiol 104 Pages: 766-772
  • Peer Reviewed
• [Journal Article] Augmentation of neovascularizaiton in hindlimb ischemia by combined transplantation of human embryonic stem cells-derived endothelial and mural cells. (2008)
  • Author(s): Yamahara K, Sone M, Itoh H, Yamashita JK, Nakao K.他6名
  • Journal Title: PLoS One (印刷中)
  • Peer Reviewed
• [Journal Article] Cyclic strain induces mouse embryonic stem cell differentiation into vascular smooth muscle cells by activating PDGF receptor {beta}. (2008)
  • Author(s): Shimizu N, Yamamoto K, Obi S, Kumagaya S, Masumura T, Shimano Y, Naruse K, YamashitaJK, Igarashi T, Ando J.
  • Journal Title: J Appl Phvsiol (印刷中)
  • Peer Reviewed
• [Journal Article] Furuse M. Identification of adherens junction-associated GTPase activating proteins by the fluorescence localization-based expression cloning. (2008)
  • Author(s): Matsuda M, Kobayashi Y, Masuda S, Adachi M, Watanabe T, Yamashita JK, Nishi E, Tsukita S,
  • Journal Title: Exp Cell Res (印刷中)
  • Peer Reviewed
• [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
• [Journal Article] Hyperpolariaation-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
  • Peer Reviewed
• [Journal Article] A pathway for differentiation of human embryonic stem cells to vascular cell components and their potential for vascular regeneration. (2007)
  • Author(s): Solle M, Itoh h, Yamahara K, Yamashita JK, 他16名
  • Journal Title: Arterioscler Thromb Vasc Biol 27 Pages: 2127-2134
  • Peer Reviewed
• [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
  • Peer Reviewed
• [Journal Article] Two populations of Thyl-positfve mesenchymal cells regulate the in vitro maturation of hepatic progenitor cells. (2007)
  • Author(s): Kamo N, (他7名) Yamashita JK, Kubo H, Ikai I.
  • Journal Title: Am J Physiol Gastroiiltest Liver Phvsiol 292
  • Peer Reviewed
• [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): Yamashita JK.
  • Organizer: 私学理科研究会二学期例会(招請講演)
  • Place of Presentation: 京都
  • Year and Date: 2008-12-25
• [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細胞を用いた心血管分化再生研究. (2008)
  • Author(s): Yamashita JK.
  • Organizer: 熊本Science Frontier研究会(特別講演)
  • Place of Presentation: 熊本
  • 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] ES細胞及びiPS細胞からの心血管分化 (2008)
  • Author(s): Yamashita JK.
  • Organizer: BMB2008シンポジウム : lSl多能性幹細胞を規定する因子群-臨床応用を見据えて-(招請講演)
  • Place of Presentation: 神戸
  • 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] 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 llscular Medical Science and Innovative Therapy" (invited).
  • Place of Presentation: Kumanioto
  • 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] Specific Expansion of Cardiac Progenitors and Cardiomyocytes from ES and iPS Cells. (2008)
  • Author(s): Yamashita JK.
  • Organizer: The Second International Cell Therapy Conference(invited)
  • 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] 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(招請講演)
  • Place of Presentation: 京都
  • 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: 佐賀・生活習慣病フォーラム2008 (特別講演)
  • Place of Presentation: 佐賀
  • 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: 心血管再生先端治療フォーラム(特別講演)
  • Place of Presentation: 東京
  • 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] 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)
• [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
• [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)
• [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
• [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)
• [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
• [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)
• [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)
• [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)
• [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)
• [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(招請講演)
  • Place of Presentation: 御殿場
• [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(invited).
  • Place of Presentation: 金沢
• [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細胞を用いた新しい構成的アプローチによる血管分化多様化 (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」(オーガナイザー)
  • Place of Presentation: 横浜
  • 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] 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
  • 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
• [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. (Invited)
  • Place of Presentation: Keystone, USA
  • 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
  • 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
  • Publisher: A linkage in the developmental pathway of vascular and hematopoietic cells.In Tanaka K, Davie EW
• [Book] Recent Advances in Thrombosis and Hemostasis 2008. Part 5 (2008)
  • Author(s): Yamashi ta JK.
  • Publisher: Springer
• [Remarks] 京都大学再生医科学研究所附属幹細胞医学研究センター幹細胞分化制御研究領域
  • URL: http://www.frontier.kyoto-u.ac.jp/es02/
• [Remarks] 京都大学 再生医科学研究所 附属幹細胞医学研究センター幹細胞分化制御研究領域
• [Remarks]
  • URL: http://www.frontier.kyoto-u.ac.jp/es02/
• [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
  • Filing Date: 2008-08-29
• [Patent(Industrial Property Rights)] Efficient production and use of highly cardiogenitors progenitors and cardiomyocyies from eoibryonic and induced pluripotent stem cells (2008)
  • Inventor(s): 山下潤顔培実
  • Industrial Property Rights Holder: 京都大学
  • Filing Date: 2008-08-29
  • Overseas