Role and therapeutic potential of SDF-1/CXCR4 system in cardiovascular diseases

• Project/Area Number: 19590857
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Shinshu University
• Principal Investigator: TAKAHASHI Masafumi Shinshu University, 大学院・医学系研究科, 准教授 (40296108)
• Co-Investigator(Kenkyū-buntansha): IKEDA Uichi 信州大学, 医学系・研究科, 教授 (30221063) ; ISE Hirohiko 信州大学, 医学系・研究科, 助教 (10324253)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2007: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: ケモカイン / 血管新生 / 虚血 / 骨髄細胞 / 炎症 / 移植 / サイトカイン / 心血管病 / 幹細胞

Research Abstract

我々は、自己骨髄細胞を用いて重症下肢虚血や心筋虚血患者を対象に血管再生療法を行い、その有効性と安全性を報告してきたが、本治療法では全身麻酔下で骨髄細胞を採取する必要があり侵襲が大きいことや、治療を行ってもその効果が十分ではない症例があることを経験してきた。そこで、治療の有効性を高め、かつ患者への侵襲の少ない新たな心血管再生療法の確立を目的として、ケモカインSDF-1とその受容体であるCXCR4(SDF-1/CXCR4システム)に着目して研究を行ってきた。

Research Products

• [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] 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] 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] Critical role of bone marrow-derived ASC, an inflammasome adaptor molecule, in neointimal formation after vascular injury in mice (2008)
  • Author(s): Takahashi M*, Yajima N(equally contribution), 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] Deficiency of tumor necrosis factor-alpha and interferon-gamma in bone marrow cells synergistically inhibits neointimal formation following vascular injury (2008)
  • Author(s): Murayama H, Takahashi M*, Takamoto M, Shiba Y, Ise H, Koyama J, Tagawa Y, Iwakura Y, Ikeda U
  • Journal Title: Cardiovasc Res 80 Pages: 175-180
  • Peer Reviewed
• [Journal Article] High-mobility group box 1 protein(HMBG1)in ischemic heart disease: beneficial or deleterious (2008)
  • Author(s): Takahashi M*
  • Journal Title: (Editorial)Cardiovasc Res 80 Pages: 5-6
  • Peer Reviewed
• [Journal Article] MCP-1 induces cardioprotection against ischemia/reperfusion injury : Role of reactive oxygen species (2008)
  • Author(s): Morimoto H, Hirose M, Takahashi M*, Kawaguchi M, Ise H, Kolattukudy PE, Yamada M, Ikeda U
  • Journal Title: Cardiovasc Res 78 Pages: 554-562
  • Peer Reviewed
• [Journal Article] Models for the study of angiogenesis (2008)
  • Author(s): Shiba Y*, Takahashi M, Ikeda U
  • Journal Title: Curr Pharm Design 14 Pages: 371-377
  • Peer Reviewed
• [Journal Article] Critical role of bone marrow-derived ASC, an inflammasome adaptormolecule, in neointimal formation after vascular injury in mice. (2008)
  • Author(s): Takahashi M^*, Yajima N (equallycontribution), 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] Deficiency of tumor necrosis factor-alpha and interferon-gamma in bone marrow cells synergistically inhibits neointimal formation following vascular injury. (2008)
  • Author(s): Murayama H, Takahashi M^*. Takamoto M, Shiba Y, Ise H, Koyama J, Tagawa Y, Iwakura Y, Ikeda U.
  • Journal Title: Cardiovasc Res 80 Pages: 175-180
  • Peer Reviewed
• [Journal Article] High-mobility group box 1 protein (HMBG1) in ischemic heart disease : beneficial or deleterious. (Editorial) (2008)
  • Author(s): Takahashi M^*.
  • Journal Title: Cardiovasc Res 80 Pages: 5-6
  • Peer Reviewed
• [Journal Article] MCP-1 induces cardioprotection against ischemia/reperfusion injury : Role of reactive oxygen species. (2008)
  • Author(s): Morimoto H, Hirose M, Takahashi M*. Kawaguchi M, Ise H, Kolattukudy PE, Yamada M, Ikeda U.
  • Journal Title: Cardiovasc Res 78 Pages: 554-562
  • Peer Reviewed
• [Journal Article] Models for the study of angiogenesis. (2008)
  • Author(s): Shiba Y^*, Takahashi M, Ikeda U.
  • Journal Title: Curr Pharm Design 14 Pages: 371-377
  • Peer Reviewed
• [Journal Article] M-CSF accelerates neointimal formation in the early phase after vascular injury in mice: The critical role of the SDF-1-CXCR4system. (2007)
  • Author(s): Shiba Y, Takahashi M, Yoshioka T, Yajima N, Morimoto H, Izawa A, Ise H, Hatake K, Motoyoshi K, Ikeda U.
  • Journal Title: Arterioscler Thromb Vase Biol 27 Pages: 283-289
  • Peer Reviewed
• [Journal Article] Bone marrow-derived CXCR4^+ cells mobilized by M-CSF participate in the prevention of cardiac dysfunction and remodeling after myocardial in farction in mice. (2007)
  • Author(s): Morimoto H, Takahashi M, Shiba Y, Izawa A, Ise H, Hongo M, Hatake K, Motoyoshi K, Ikeda U.
  • Journal Title: Am J Pathol 171 Pages: 755-766
  • Peer Reviewed
• [Journal Article] Adenoassociated virus-mediated prostacyclin synthase expression prevents pulmonary arterial hypertension in rats. (2007)
  • Author(s): Ito T, Okada T, Mimuro J, Miyashita H, Uchibori R, Urabe M, Mizukami H, Kume A, Takahashi M, IKeda U, Sakata Y, Shimada K, Ozawa K.
  • Journal Title: Hypertension 50 Pages: 531-536
  • Peer Reviewed
• [Journal Article] Erythropoietin attenuates the development of experimental autoimmune myocarditis. (2007)
  • Author(s): Hirose S, Takahashi M, Ogawa R, Morimoto H, Izawa A, Sato H, Ise H, Hongo M, Ikeda U
  • Journal Title: Cardiovasc Drug Ther 21 Pages: 17-27
  • Peer Reviewed
• [Journal Article] A novel sphingosine-l-phosphate receptor agonist KRP-203 attenuates ratautoimmune myocarditis. (2007)
  • Author(s): Ogawa R, Takahashi M, Hirose S, Morimoto H, Ise H, Murakami T, Yasue T, Kuriyama K, Hongo M, Kobayashi E, Ikeda U.
  • Journal Title: Biochem Biophys Res Commun 36 Pages: 621-628
  • Peer Reviewed
• [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、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大会
  • Place of Presentation: 神戸
• [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、後藤光昭、麻生真一、池田宇一
  • Organizer: 日本バイオマテリアル学会(シンポジウム)
  • Place of Presentation: 東京
• [Presentation] Therapeutic angiogenesis by mononuclear cell implantation for critical digit ischemia of patients with connective tissue diseases (2008)
  • Author(s): Takahashi M, Ishigatsubo Y, Fujimoto K, Miyamoto M, Minota S, Horie T, Aizawa Y, Amano J, Murohara T, Matsubara H, Ikeda U
  • Organizer: American Heart Association Scientific Sessions
  • Place of Presentation: New Orleans
• [Presentation] Role of interleukin-6 and its crosstalk with AT1R in acute and chronic rejection of murine cardiac allografts (2008)
  • Author(s): Izawa A, Takahashi M, Ise H, Morimoto H, Yajima N, Tagawa Y, Ikeda U
  • Organizer: American Heart Association Scientific Sessions
  • Place of Presentation: New Orleans
• [Presentation] Role of an Inflammasome adaptor molecule ASC in myocardial ischemia-reperfusion injury (2008)
  • Author(s): Kawaguchi M, Takahashi M, Hata T, Takahashi Y, Morimoto H, Ise H, Sagara J, Hongo M, Taniguchi S, Ikeda U
  • Organizer: American Heart Association Scientific Sessions
  • Place of Presentation: New Orleans
• [Presentation] Critical role of Th17-CD4+ T cells in angiogenic response to hindlimb ischemia in mice (2008)
  • Author(s): Hata T, Takahashi M, Kawaguchi T, Kashima Y, Shiba Y, Ise H, Hida S, Iwakura Y, Taki S, Ikeda U
  • Organizer: American Heart Association Scientific Sessions
  • Place of Presentation: New Orleans
• [Presentation] Double Deficiency of Tumour Necrosis Factor-α and Interferon-γ in Bone Marrow-derived Cells Prevents Neointimal formation in a Murine Model of Vascular Injury (2008)
  • Author(s): Murayama H, Takahashi M, Shiba Y, Ise H, Takamoto M, Tagawa Y, Iwakura Y, Ikeda U
  • Organizer: American Heart Association Scientific Sessions
  • Place of Presentation: New Orleans
• [Presentation] 自己骨髄細胞移植による難治性血管炎に対する血管新生療法 (2008)
  • Author(s): 高橋将文、石ヶ坪良明、藤本和輝、宮本正章、相澤義房、天野純、簑田清次、室原豊明、松原弘明、池田宇一
  • Organizer: 第49回日本脈管学会総会(シンポジウム)
  • Place of Presentation: 東京
• [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: 東京
• [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: 横浜
• [Presentation] Impact of TNF-alpha and IFN-gamma on neointimal formation after vascular injury in mice (2008)
  • Author(s): Murayama T, Takahashi M, Shiba Y, Ise H, Tagawa Y, Takamoto M, Ikeda U
  • Organizer: 第72回日本循環器学会
  • Place of Presentation: 福岡
• [Presentation] Upregulation of CXCR4 in bone marrow cells enhances the angiogenic potencyin a murine model of hindlimb ishemia (2008)
  • Author(s): Shiba Y, Takahashi M, Ise H, Ikeda U
  • Organizer: 第72回日本循環器学会
  • Place of Presentation: 福岡
• [Presentation] Cardioprotection of MCP-1 against ischemia/reperfusion injury is mediated through a redox oxygen species (ROS)-dependent but KATP channel-independent pathway (2008)
  • Author(s): Morimoto H, Takahashi M, Hirose M, Kawaguchi M, Ise H, Yamada M, Ikeda U
  • Organizer: 第72回日本循環器学会
  • Place of Presentation: 福岡
• [Presentation] Clinical Significance of sleep-desordered breathing(SDB)in a large population of Japanese patients : Efficacy of CPAP therapy in SDB-associated arrhythmias (2008)
  • Author(s): Abe H, Takahashi M, Tsukioka K, Kitahara H, Tsunemoto H, Suzuki J, Yaegashi H, Eda S, Yamazaki K, Kamikozawa M, Ikeda U
  • Organizer: 第72回日本循環器学会
  • Place of Presentation: 福岡
• [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、後藤光昭、麻生真一、池田宇一
  • Organizer: 第7回日本再生医療学会総会
  • Place of Presentation: 名古屋
• [Presentation] Therapeutic angiogenesis by mononuclear cell implantation for critical digit ischemia of patients with connective tissue diseases. (2008)
  • Author(s): Takahashi M, Ishigatsubo Y, Fujimoto K, Miyamoto M, Minota S, Horie T, Aizawa Y, Amano J, Murohara T, Matsubara H, Ikeda U.
  • Organizer: American Heart Association Scientific Sessions
  • Place of Presentation: New Orleans
• [Presentation] Role of interleukin-6 and its crosstalk with AT1R in acute andchronic rejection of murine cardiac allografts. (2008)
  • Author(s): Izawa A, Takahashi M, Ise H, Morimoto H, Yajima N, Tagawa Y, Ikeda U.
  • Organizer: American Heart Association Scientific Sessions
  • Place of Presentation: New Orleans
• [Presentation] Role of an Inflammasome adaptor molecule ASC in myocardial ischemia-reperfusion injury. (2008)
  • Author(s): Kawaguchi M, Takahashi M, Hata T, Takahashi Y, Morimoto H, Ise H, Sagara J, Hongo M, Taniguchi S, Ikeda U.
  • Organizer: American Heart Association Scientific Sessions
  • Place of Presentation: New Orleans
• [Presentation] Critical role of Thl7-CD4+T cells in angiogenic response to hindlimb ischemia in mice. (2008)
  • Author(s): Hata T, Takahashi M, Kawaguchi T, Kashima Y, Shiba Y, Ise H, Hida s, Iwakura Y, Taki S, Ikeda U.
  • Organizer: American Heart Association Scientific Sessions
  • Place of Presentation: New Orleans
• [Presentation] Double Deficiency of Tumour Necrosis Factor-□ and Interferon-□ in Bone Marrow-derived Cells Prevents Neointimal formation in a Murine Model of Vascular Injury. (2008)
  • Author(s): Murayama H, Takahashi M, Shiba Y, Ise H, Takamoto M, Tagawa Y, Iwakura Y, Ikeda U.
  • Organizer: American Heart Association Scientific Sessions
  • Place of Presentation: New Orleans
• [Presentation] 自己骨髄細胞移植による難治性血管炎に対する血管新生療法. (2008)
  • Author(s): 高橋将文, 石ヶ良明, 藤本和輝, 宮本正章, 相澤義房, 天野純, 簑田清次, 室原豊明, 松原弘明, 池田宇一
  • Organizer: 第49回日本脈管学会総会
  • Place of Presentation: 東京
• [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, 後藤光昭, 麻生真一, 池田宇一
  • Organizer: 日本バイオマテリアル学会
  • Place of Presentation: 東京
• [Presentation] Impact of TNF-alpha and IFN-gamma on neointimal formation after vascular injury in mice. (2008)
  • Author(s): Murayama T, Takahashi M, Shiba Y, Ise H, Tagawa Y, Takamoto M, Ikeda U
  • Organizer: 第72回日本循環器学会
  • Place of Presentation: 福岡
• [Presentation] Upregulation of CXCR4 in bone marrow cells enhances the angiogenic potencyin a murine model of hindlimb ishemia. (2008)
  • Author(s): Shiba Y, Takahashi M, Ise H, Ikeda U
  • Organizer: 第72回日本循環器学会
  • Place of Presentation: 福岡
• [Presentation] Cardioprotection of MCP-1 against ischemia/reperfusion injury is mediated through a redox oxygen species (ROS)-dependent but K_<ATP> channel-iadependent pathway. (2008)
  • Author(s): Morimoto H, Takahashi M, Hirose M, Kawaguchi M, Ise H, Yamada M, Ikeda U
  • Organizer: 第72回日本循環器学会
  • Place of Presentation: 福岡
• [Presentation] Clinical Significance of sleep-desordered breathing (SDB)in a large population of Japanese patients : Efficacy of CPAP therapy in SDB-associated arrhythmias. (2008)
  • Author(s): Abe H, Takahashi M, Tsukioka K, Kitahara H, Tsunemoto H, Suzuki J, Yaegashi H, Eda S, Yamazaki K, Kamikozawa M, Ikeda U
  • Organizer: 第72回日本循環器学会
  • Place of Presentation: 福岡
• [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: 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: 東京
• [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, 後藤光昭, 麻生真一, 池田宇一
  • Organizer: 第7回日本再生医療学会総会
  • Place of Presentation: 名古屋
• [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, 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
• [Presentation] Apregulation of CXCR4+ in Bone Marrow Cells Enhanced the Angiogenic Potencyin a Murine Model of Hindlimb Ischemia. (2008)
  • Author(s): Shiba Y, Takahashi M, Ise H, lkeda U
  • Organizer: 第72回日本循環器学会
  • Place of Presentation: 福岡
• [Presentation] CXCR4-posotive cells as a new souce for therapeutic angiogenesis. (2007)
  • Author(s): 柴 祐司、高橋将文
  • Organizer: 第5回LifeScience Frontiers
  • Place of Presentation: 東京
  • Year and Date: 2007-07-21
• [Presentation] Bone marrow-derived CXCR4^+ cells a New Source for therapeutic angiogenesis. (2007)
  • Author(s): 柴 祐司、高橋将文、山田亜衣、伊澤 淳、森本 創、伊勢裕彦、池田宇一
  • Organizer: 第7回心血管再生先端治療フォーラム
  • Place of Presentation: 東京
  • Year and Date: 2007-06-30
• [Presentation] Bone Marrow-derived CXCR4+ Cells ax a New Source for Therapeutic Angiogenesis. (2007)
  • Author(s): Shiba Y, Takahashi M, Izawa A, Morimoto H, Ise H, Ikeda U
  • Organizer: AHA 2007
  • Place of Presentation: Orlando(USA)