Development of cell, gene and drug delivery system to the cardiovascular tissue using a novel cell-surface lectin.

• Project/Area Number: 20390222
• 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: Shinshu University
• Principal Investigator: IKEDA Uichi Shinshu University, 医学系研究科, 教授 (30221063)
• Co-Investigator(Kenkyū-buntansha): KOYAMA Jun 信州大学, 医学系研究科, 准教授 (10303463) ; IZAWA Atsushi 信州大学, 医学系研究科, 助教 (50464095) ; 高橋 将文 信州大学, 医学系研究科, 准教授 (40296108)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000); Fiscal Year 2010: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2009: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2008: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
• Keywords: 再生医療 / 糖鎖 / 遺伝子 / 心筋梗塞 / 動脈硬化 / 心筋細胞

Research Abstract

We found a novel function of vimentin and desmin of cardiovascular tissues by which these proteins interact with physiological GlcNAc-bearing ligands on the cell surface through their GlcNAc-binding lectin-like properties. Cell surface coating of bone marrow cells with GlcNAc promoted adhesion of these cells to cardiac myocytes and their regeneration to cardiac myocytes, and this would be useful for the treatment of cardiovascular disease with bone marrow implantation.

Research Products

• [Journal Article] Inflammasome activation of cardiac fibroblasts is essential for myocardial ischemia/reperfusion injury. (2011)
  • Author(s): Kawaguchi M, Takahashi M, Hata T, Kashima Y, Usui F, Morimoto H, Izawa A, Takahashi Y, Masumoto J, Koyama J, Hongo M, Noda T, Nakayama J, Sagara J, Taniguchi S, Ikeda U.
  • Journal Title: Circulation 123 Pages: 594-604
  • Peer Reviewed
• [Journal Article] Inflammasome activation of cardiac fibroblasts is essential for myocardial ischemia/reperfusion injury (2011)
  • Author(s): Kawaguchi M, Takahashi M, Hata T, et al.
  • Journal Title: Circulation Volume: 123 Pages: 594-604
  • Peer Reviewed
• [Journal Article] Vimentin and desmin possess GlcNAc-binding lectin-like properties on cell surfaces. (2010)
  • Author(s): Ise H, Kobayashi S, Goto M, Sato T, Kawakubo M, Takahashi M, Ikeda U, Akaike T.
  • Journal Title: Glycobiology 20 Pages: 843-864
  • Peer Reviewed
• [Journal Article] Vimentin and desmin possess GlcNAc-binding lectin-like properties on cell surfacres (2010)
  • Author(s): Ise H, Kobayashi S, Soto M, et al.
  • Journal Title: Glycobiology Volume: 20 Pages: 843-864
  • Peer Reviewed
• [Journal Article] (2010)
  • Author(s): 伊澤淳、池田宇一
  • Journal Title: 心筋梗塞の再発予防(循環器疾患最新の治療)(南江堂) Pages: 126-128
• [Journal Article] Therapeutic neovascularization by the implantation of autologous mononuclear cells in patients with connective tissue diseases. (2009)
  • Author(s): Takahashi M, Izawa A, Ishigatsubo Y, Fujimoto K, Miyamoto M, Horie T, Aizawa Y, Amano J, Minota S, Murohara T, Matsubara H, Ikeda U.
  • Journal Title: Curr Pharm Design 15 Pages: 2778-2783
  • Peer Reviewed
• [Journal Article] Notch signaling regulates the differentiation of bone marrow-derived cells into smooth muscle-like cells during arterial lesion formation. (2009)
  • Author(s): Doi H, Iso T, Shiba Y, Sato H, Yamazaki M, Oyama Y, Akiyama H, Tanaka T, Tomita T, Arai M, Takahashi M, Ikeda U, Kurabayashi M.
  • Journal Title: Biochem Biophys Res Commun 381 Pages: 654-659
  • Peer Reviewed
• [Journal Article] Systemic delivery of IL-10 by an AAV vector prevents vascular remodeling and end-organ damage in stroke-prone spontaneously hypertensive rat. (2009)
  • Author(s): Nomoto T, Okada T, Shimazaki K, Yoshioka T, Nonaka-Sarukawa M, Ito T, Takeuchi K, Katsura KI, Mizukami H, Kume A, Ookawara S, Ikeda U, Katayama Y, Ozawa K.
  • Journal Title: Gene Ther 16 Pages: 383-391
  • Peer Reviewed
• [Journal Article] Surface coating of bone marrow cells with N-acetylglucosamine for bone marrow implantation therapy. (2009)
  • Author(s): Kobayashi S, Ise H, Takahashi M, Goto M, Akaike T, Ikeda U.
  • Journal Title: Biomaterials 30 Pages: 574-582
  • Peer Reviewed
• [Journal Article] Bone marrow CXCR4 induction by cultivation enhances therapeutic angiogenesis. (2009)
  • Author(s): Shiba Y, Takahashi M, Hata T, Murayama H, Morimoto H, Ise H, Nagasawa T, Ikeda U.
  • Journal Title: Cardiovasc Res 81 Pages: 169-177
  • Peer Reviewed
• [Journal Article] Therapeutic neovascularization by the implantation of autologous mononu clear cells in patients with connective tissue diseases. (2009)
  • Author(s): Takahashi M, Izawa A, Ishigatsubo Y, Fujimoto K, Miyamoto M, Horie T, Aizawa Y, Amano J, Minota S, Murohara T, Matsubara H, Ikeda U
  • Journal Title: Curr Pharm Des 15 Pages: 2778-2783
  • Peer Reviewed
• [Journal Article] Noninvasive evaluation of coronary endothelial function following sirolimus-eluting stent implantation by using positron emission tomography. (2009)
  • Author(s): Horigome M, Kumazaki S, Hattori N, Kasai H, Horigome M, Aizawa K, Izawa A, Tomita T, Tsutsui H, Koyama J, Sakurai S, Ikeda U.
  • Journal Title: Cardiology 114 Pages: 157-163
  • Peer Reviewed
• [Journal Article] Notch signaling regulates the differentiation of bone marrow-derived cells into smooth muscle-like cells during arterial lesion formation. (2009)
  • Author(s): Doi H, Iso T, Shiba Y, Sato H, Yamazaki M, Oyama Y, Akiyama H, Tanaka T, Tomita T, Arai M, Takahashi M, Ikeda U, Kurabayashi M
  • Journal Title: Biochem Biophys Res Commun 381 Pages: 654-659
  • Peer Reviewed
• [Journal Article] Surface coating of bone marrow cells with N-acetylglucosamine for bone marrow implantation therapy. (2009)
  • Author(s): Kobayashi S, Ise H, Takahashi M, Goto M, Akaike T, Ikeda U
  • Journal Title: Biomaterials 30 Pages: 574-582
  • Peer Reviewed
• [Journal Article] Systemic delivery of IL-10 by an AAV vector prevents vascular remodeling and end-organ damage in stroke-prone spontaneously hypertensive rat. (2009)
  • Author(s): Nomoto T, Okada T, Shimazaki K, Yoshioka T, Nonaka-Sarukawa M, Ito T, Takeuchi K, Katsura KI, Mizukami H, Kume A, Ookawara S, Ikeda U, Katayama Y, Ozawa K
  • Journal Title: Gene Ther 16 Pages: 383-391
  • Peer Reviewed
• [Journal Article] Bone marrow CXCR4 induction by cultivation enhances therapeutic angio genesis. (2009)
  • Author(s): Shiba Y, Takahashi M, Hata T, Murayama H, Morimoto H, Ise H, Nagasawa T, Ikeda U
  • Journal Title: Cardiovasc Res 81 Pages: 169-177
  • Peer Reviewed
• [Journal Article] (2009)
  • Author(s): 池田宇一
  • Journal Title: 動脈疾患(内科確定診断完全マスター)(メディカルビュー社) Pages: 124-130
• [Journal Article] (2009)
  • Author(s): 伊澤淳、池田宇一
  • Journal Title: コレステロールと末梢動脈(コレステロール-基礎から臨床へ-)(ライフサイエンス出版) Pages: 81-87
• [Journal Article] Bone marrow CXCR4 induction by cultivation enhances therapeutic angiogenesis. (2009)
  • Author(s): Shiba Y, Takahashi M, Hata T, Murayama H, Morimoto H, Ise H, Nagasawa T, Ikeda U
  • Journal Title: Cardiovasc Res 81 Pages: 167-177
  • Peer Reviewed
• [Journal Article] Critical role of bone marrow-derived ASC, an inflammasome adaptor molecule, in neolntimal formation after vascular injuryin mice. (2008)
  • Author(s): Yajima N, Takahashi M, Morimoto H, Shiba Y, Takahashi Y, Masumoto J, Ise H, J Sagara, Nakayama J, Taniguchi S, Ikeda U
  • Journal Title: Circulation 117 Pages: 3079-3087
  • Peer Reviewed
• [Journal Article] Changes in angiogenesis-related factors in serum following autologous bone marrow cell implantation for severe limbischemia. (2008)
  • Author(s): Tachi Y, Fukui D, Wada Y, Koshikawa M, Shimodaira s, Ikeda U, Amano J
  • Journal Title: Exp Opin Biol Ther 8 Pages: 705-712
  • Peer Reviewed
• [Presentation] 末梢動脈疾患の未来治療:細胞療法 (2010)
  • Author(s): 池田宇一
  • Organizer: 第34回金澤医師会学術セミナー
  • Place of Presentation: 金沢市 招待講演
  • Year and Date: 2010-08-02
• [Presentation] Vascular regeneration therapy for peripheral occlusive disease and collagen disorders. (2010)
  • Author(s): 池田宇一
  • Organizer: 第10回CCTシンポジウム
  • Place of Presentation: 神戸市 招待講演
  • Year and Date: 2010-01-29
• [Presentation] Vascular regeneration therapy for peripheral occlusive disease and collagen disorders. (2010)
  • Author(s): 池田宇一
  • Organizer: 第10回CCTシンポジウム
  • Place of Presentation: 神戸
  • Year and Date: 2010-01-29
• [Presentation] Critical role of hyaluronan derived from vascular smooth muscle cells in neointimal formation after vascular injury. (2010)
  • Author(s): Kashima Y, Takahashi M, Hata T, Kawaguchi K, Izawa A, Ikeda U
  • Organizer: AHA scientific sessions 2010
  • Place of Presentation: in Chicago.
• [Presentation] Inflammasome activation in cardiac fivroblasts triggers initiation of myocardial ischemia-reperfusion injury. (2010)
  • Author(s): Kawaguchi M, Takahashi M, Hata T, Kashima Y, Izawa A, Takahashi Y, Sagara J, Taniguchi S, Ikeda U
  • Organizer: 第74回日本循環器学会総会
  • Place of Presentation: 国立京都国際会館
• [Presentation] Contribution of CD4+-Th17 cells to angiogenesis following hindlimb ischemia in mice. (2010)
  • Author(s): Hata T, Takahashi M, Kawaguchi M, Kashima Y, Hida S, Izawa A, Taki S, Iwakura Y, Ikeda U
  • Organizer: 第74回日本循環器学会総会
  • Place of Presentation: 国立京都国際会館
• [Presentation] Critical role of hyaluronan derived from vascular smooth muscle cells in neointimal formation after vascular injury. (2010)
  • Author(s): Kashima Y, Takahashi M, Hata T, Kawaguchi M, Izawa A, Itano N, Taniguchi S, Ikeda U
  • Organizer: 第74回日本循環器学会総会
  • Place of Presentation: 国立京都国際会館
• [Presentation] Critical Role of Hyaluronan Derived From Vascular Smooth Muscle Cells in Neointimal Formation After Vascular Injury. (2010)
  • Author(s): Kashima Y, TakahashiM, Hata T, Kawaguchi K, Izawa A, Ikeda U.
  • Organizer: AHA scientific sessions 2010
  • Place of Presentation: Chicago
• [Presentation] 末梢動脈疾患の未来治療:細胞療法 (2009)
  • Author(s): 池田宇一
  • Organizer: 第34回金沢医師会学術セミナー
  • Place of Presentation: 金沢
  • Year and Date: 2009-08-02
• [Presentation] 糖鎖工学を利用した骨髄幹細胞の心臓ターゲッティング法の開発 (2008)
  • Author(s): 小林聡、伊勢裕彦、高橋将文、後藤光昭、麻生真一、池田宇一
  • Organizer: Cardiovascular Medicine 21/第8回フォーラム
  • Place of Presentation: 東京国際フォーラム
  • Year and Date: 2008-08-02
• [Presentation] 糖鎖工学を利用した骨髄幹細胞の心臓ターゲッティング法の開発. (2008)
  • Author(s): 小林聡, 伊勢裕彦, 高橋将文, 後藤光昭, 麻生真一, 池田宇一
  • Organizer: Cardiovascular Medicine 21/第8回フォーラム
  • Place of Presentation: 東京国際フォーラム
  • Year and Date: 2008-08-02
• [Presentation] Development of the Targeting for Myocardium by Artificial Glycoside-coated Bone Marrow Cells.(人工的な糖鎖修飾を行った骨髄細胞の心筋組織へのターゲティング法の開発) (2008)
  • Author(s): 小林聡, 伊勢裕彦, 高橋将文, 後藤光昭, 麻生真一, 池田宇一
  • Organizer: 第31回日本分子生物学会・第18回日本生化学学会合同大会
  • Place of Presentation: 神戸ポートアイランド
• [Presentation] 人工的な糖鎖修飾を行った骨髄細胞の心筋組織へのターゲッティング法の開発 (2008)
  • Author(s): 小林聡、伊勢裕彦、高橋将文、麻生真一、後藤光昭、赤池敏宏、池田宇一
  • Organizer: 日本バイオマテリアル学会シンポジウム2008
  • Place of Presentation: 東京大学本郷キャンパス
• [Presentation] 細胞骨格分子デスミン・ビメンチンの細胞膜上の発現とN-アセチルグルコサミン結合活性 (2008)
  • Author(s): 伊勢裕彦、小林聡、高橋将文、伊勢真美子、池田宇一
  • Organizer: 第29回日本炎症・再生医学会
  • Place of Presentation: 都市センターホテル
• [Presentation] Desmin and vimentin have N-acetylglucosamine-binding lectinic properties and are expressed on the cell surface. (2008)
  • Author(s): 伊勢裕彦, 小林聡, 高橋将文, 麻生真一, 赤池敏宏, 池田宇一
  • Organizer: 第60回日本細胞生物学会
  • Place of Presentation: パシフィコ横浜
• [Presentation] Desmin and vimentin have N-acetylglucosamine-binding lectinic properties and are expressed on the cell surface. (2008)
  • Author(s): Ise H, Kobayashi S, Takahashi M, Aso S, Akaike T, Ikeda U
  • Organizer: 第60回日本細胞生物学会
  • Place of Presentation: パシフイコ横浜
• [Presentation] 細胞骨格分子デスミン・ビメンチンの細胞膜上の発現とN-アセチルグルコサミン結合活性. (2008)
  • Author(s): 伊勢裕彦, 小林聡, 高橋将文, 伊勢真美子, 池田宇一
  • Organizer: 第29回日本炎症・再生医学会
  • Place of Presentation: 都市センターホテル
• [Presentation] 人工的な糖鎖修飾を行った骨髄細胞の心筋組織へのクーゲツティング法の開発. (2008)
  • Author(s): 小林聡, 伊勢裕彦, 高橋将文, 麻生真一, 後藤光昭, 赤池敏宏, 池田宇一
  • Organizer: 日本バイオマテリアル学会シンポジウム2008
  • Place of Presentation: 東京大学本郷キャンパス
• [Presentation] Development of the Targeting for Myocardium by Artificial Glycoside-coated Bone Marrow Cells. (人工的な糖鎖修飾を行った骨髄細胞の心筋組織へのターゲティング法の開発) (2008)
  • Author(s): Satoshi Kobayashil, Hirohiko Ise, Masafumi Takahashil, Mitsuaki Goto, Shinichi Aso, Uichi Ikeda
  • Organizer: 第31回日本分子生物学会・第18回日本生化学会学会合同大会
  • Place of Presentation: 神戸ポートアイランド
• [Book] 心筋梗塞の再発予防(循環器疾患最新の治療) (2010)
  • Author(s): 伊澤淳、池田宇一
  • Publisher: 南江堂、東京
• [Book] 血栓溶解薬(脈管専門医のための臨床脈管学(日本脈管学会編)) (2010)
  • Author(s): 熊崎節央、池田宇一
  • Total Pages: 125
  • Publisher: メディカルトリビューン
• [Book] 動脈疾患 内科確定診断完全マスター (2009)
  • Author(s): 池田宇一
  • Publisher: メジカルビュー社、東京
• [Book] コレステロールと末梢動脈(コレステロール-基礎から臨床へ-) (2009)
  • Author(s): 伊澤淳、池田宇一
  • Publisher: ライフサイエンス出版、東京