Therapeutic angiogenesis to ischemic heart disease by cell transplantation

• Project/Area Number: 16390220
• 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, Department of Organ Regeneration, Professor, 大学院医学系研究科, 教授 (30221063)
• Co-Investigator(Kenkyū-buntansha): AMANO Jun Shinshu University, Department of Surgery, Professor, 医学部, 教授 (20138283) ; TAKAHASHI Masafumi Shinshu University, Department of Organ Regeneration, Associate Professor, 大学院医学系研究科, 助教授 (40296108) ; ISE Hirohiko Shinshu University, Department of Organ Regeneration, Assistant Professor, 大学院医学系研究科, 助手 (10324253)
• Project Period (FY): 2004 – 2006
• Project Status: Completed (Fiscal Year 2006)
• Budget Amount: ¥13,800,000 (Direct Cost: ¥13,800,000); Fiscal Year 2006: ¥4,100,000 (Direct Cost: ¥4,100,000); Fiscal Year 2005: ¥4,500,000 (Direct Cost: ¥4,500,000); Fiscal Year 2004: ¥5,200,000 (Direct Cost: ¥5,200,000)
• Keywords: regeneration / atherosclerosis / myocardial infarction / bone marrow / angiogenesis

Research Abstract

We have previously reported the effectiveness and safety of therapeutic angiogenesis by transplantation of autologous bone marrow mononuclear cells to ischemic limbs (Lancet 2002). In this study, we investigated whether transplantation of bone marrow-derived endothelial progenitor cells (EPCs) would also be effective in patients with ischemic heart disease. Bone marrow-derived EPCs were transplanted to the myocardium in patients with ischemic heart disease ; They received bone marrow-derived CD34^+ cell transplantation into ungraftable regions of the left ventricle with concomitant coronary artery bypass grafts (hybrid therapy). Before and 1 month after cell transplantation, we assessed the regional blood flow by single photon emission computed tomography (SPECT). The blood flow in the EPC-transplanted region as well as the grafted region was significantly increased at 1 month after cell transplantation. No side effects were observed. In this study, we demonstrated that autologous transplantation of bone marrow-derived EPCs represents a new and promising strategy for clinical application designed to revascularize the ischemic myocardium

Research Products

• [Journal Article] M-CSF accelerates neointimal formation in the early phase after vascular injury in mice : the critical role of the SDF-1-CXCR4 system. (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
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] M-CSF accelerates neointimal formation in the early phase after vascular injury in mice: the critical role of the SDF-1-CXCR4 system. (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 Vasc Biol 27 Pages: 283-289
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Cardiac overexpression of MCP-1 in transgenic mice prevents cardiac dysfunction and remodeling after myocardial infarction. (2006)
  • Author(s): Morimoto H, Takahashi M, Izawa A, Ise H, Hongo M, Kolattukudy PK, Ikeda U
  • Journal Title: Circ Res 99 Pages: 891-899
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Development of liver regenerative therapy using glycoside-modified bone marrow cells. (2006)
  • Author(s): Misawa R, Ise H, Takahashi M, Morimoto H, Kobayashi E, Miyagawa S, Ikeda U
  • Journal Title: Biochem Biophys Res Commun 342 Pages: 432-440
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] G-CSF accelerates reendothelialization and reduces neointimal formation after vascular injury in mice. (2006)
  • Author(s): Yoshioka T, Takahashi M, Shiba Y, Suzuki C, Morimoto H, Izawa A, Ise H, Ikeda U
  • Journal Title: Cardiovasc Res 70 Pages: 61-69
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Therapeutic potential of endothelial progenitor cells for cardiovascular diseases. (2006)
  • Author(s): Jia L, Takahashi M, Yoshioka T, Morimoto H, Ise H, Ikeda U
  • Journal Title: Current Vascular Pharmacology 4 Pages: 59-65
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Development of liver regenerative, therapy using glycoside-modified bone marrow cells (2006)
  • Author(s): Misawa R, Ise H, Takahashi M, Morimoto H, Kobayashi E, Miyagawa S, Ikeda U
  • Journal Title: Biochem Biophys Res Commun 342 Pages: 432-440
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] G-CSF accelerates reendothelialization and reduces neointimal formation after vascular injury in mice (2006)
  • Author(s): Yoshioka T, Takahashi M, Shiba Y, Suzuki C, Morimoto H, Izawa A, Ise H, Ikeda U
  • Journal Title: Cardiovasc Res 70 Pages: 61-69
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Therapeutic potential of endothelial progenitor cells for cardiovascular diseases (2006)
  • Author(s): Jia L, Takahashi M, Yoshioka T, Morimoto H, Ise H, Ikeda U
  • Journal Title: Current Vascular Pharmacology 4 Pages: 59-65
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Cardiac overexpression of MCP-1 in transgenic mice prevents cardiac dysfunction and remodeling after myocardial infarction. (2006)
  • Author(s): Morimoto H, Takahashi M, Izawa A, Ise H, Hongo M, Kolattukudy PK, Ikeda U.
  • Journal Title: Circ Res 99 Pages: 891-899
• [Journal Article] Mycophenolate mofetil attenuates pulmonary arterial hypertension in rats. (2006)
  • Author(s): Suzuki C, Takahashi M, Morimoto H, Izawa A, Ise H, Hongo M, Hoshikawa Y, Ito T, Miyashita H, Kobayashi E, Shimada K, Ikeda U.
  • Journal Title: Biochem Biophys Res Commun 349 Pages: 781-788
• [Journal Article] Development of liver regenerative therepy using glycoside-modified bone marrow cells. (2006)
  • Author(s): Misawa R, Ise H, Takahashi M, Morimoto H, Kobayashi E, Miyagawa S, Ikeda U.
  • Journal Title: Biochem Biophys Res Commun 342 Pages: 432-440
• [Journal Article] Collagen synthesis is requied for ascorbic acid-enhanced differentiation of mouse embryonic stem cells into cardiomyocytes. (2006)
  • Author(s): Sato H, Takahashi M, Ise H, Yamada A, Hirose S, Tagawa Y, Morimoto H, Izawa A, Ikeda U.
  • Journal Title: Biochem Biophys Res Commun 342 Pages: 107-112
• [Journal Article] Efficacy of mycophenolic acid combined with KRP-203, a novel immunomodulator, in rat heart transplantation model. (2006)
  • Author(s): Suzuki C, Takahashi M, Morimoto H, Izawa A, Ise H, Fujishiro J, Murakami T, Ishiyama J, Nakada A, Nakayama J, Shimada K, Ikeda U, Kobayashi E.
  • Journal Title: J Heart Lung Transpl 25 Pages: 302-309
• [Journal Article] G-CSF accelerates reendothelialization and reduces neointimal formation after vascular injury in mice. (2006)
  • Author(s): Yoshioka T, Takahashi M, Shiba Y, Suzuki C, Morimoto H, Izawa A, Ise H, Ikeda U.
  • Journal Title: Cardiovasc Res 70 Pages: 61-69
• [Journal Article] Changes in cardiac lipid metabolism during sepsis : The essential role of very low-density lipoprotein receptors. (2006)
  • Author(s): Jia L, Takahashi M, Morimoto H, Takahashi S, Izawa A, Ise H, Iwasaki T, Hattori H, Wu KJ, Ikeda U.
  • Journal Title: Cardiovasc Res 69(2) Pages: 545-555
• [Journal Article] Cre/loxP-mediated CTLA4IgG gene transfer induces clinically relevant immunosuppression via on-off gene recombination in vivo. (2006)
  • Author(s): Izawa A, Sano K, Takehara M, Inobe M, Suzuki J, Imamura H, Takahashi M, Ikeda U, Isobe M, Uede T.
  • Journal Title: Cardiovasc Res 69(1) Pages: 289-297
• [Journal Article] Repair of infarcted myocardium mediated by transplanted bone marrow-derived CD34^+ stem cells in a nonhuman primate model (2005)
  • Author(s): Yoshioka T, Ageyama N, Shibata H, Yasu T, Misawa Y, Takeuchi K, Matsui K, Yamamoto K, Terao K, Shimada K, Ikeda U, Ozawa K, Hanazono Y
  • Journal Title: Stem Cells 23 Pages: 355-364
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Repair of infracted myocardium mediated by transplanted bone marrow-derived CD34^+ stem cells in a nonhuman primate model (2005)
  • Author(s): Yoshioka T, Ageyama N, Shibata H, Yasu T, Misawa Y, Takeuchi K, Matsui K, Yamamoto K, Terao K, Shimada K, Ikeda U, Ozawa K, Hanazono Y
  • Journal Title: Stem Cells 23 Pages: 355-364
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Mycophenolate mofetil prevents the development of experimental autoimmune myocarditis. (2005)
  • Author(s): Kamiyoshi Y, Takahashi M, Yokoseki O, Yazaki Y, Hirose S, Morimoto H, Watanabe N, Kinoshita O, Hongo M, Ikeda U.
  • Journal Title: J Mol Cell Cardiol 39(3) Pages: 467-477
• [Journal Article] MCI-186 (edaravone), a free radical scavenger, attenuates hepatic warm ischemia-reperfusion injury in rats. (2005)
  • Author(s): Suzuki F, Hashikura Y, Ise H, Ishida A, Nakayama J, Takahashi M, Miyagawa S, Ikeda U.
  • Journal Title: Transpl Int 18(7) Pages: 844-853
• [Journal Article] Interleukin-1beta attenuates beta-very low-density lipoprotein uptake and its receptor expression in vascular smooth muscle cells. (2005)
  • Author(s): Takahashi M, Takahashi S, Suzuki C, Jia L, Morimoto H, Ise H, Iwasaki T, Hattori H, Suzuki J, Miyamori I, Kobayashi E, Ikeda U.
  • Journal Title: J Mol Cell Cardiol 38(4) Pages: 637-646
• [Journal Article] Repair of infarcted myocardium mediated by transplanted bone marrow-derived CD34+ stem cells in a nonhuman primate model. (2005)
  • Author(s): Yoshioka T, Ageyama N, Shibata H, Yasu T, Misawa Y, Takeuchi K, Matsui K, Yamamoto K, Terao K, Shimada K, Ikeda U, Ozawa K, Hanazono Y.
  • Journal Title: Stem Cells 23(3) Pages: 355-364
• [Journal Article] Decrease in circulating endothelial progenitor cells in patients with stable coronary artery disease. (2004)
  • Author(s): Eizawa T, Ikeda U, Yosioka T, Takahashi M, et al.
  • Journal Title: Heart 90 Pages: 90-90
• [Journal Article] Increase in circulating endothelial progenitor cells after aortic aneurysm repair. (2004)
  • Author(s): Eizawa T, Ikeda U, Takahashi M, et al.
  • Journal Title: Heart Vessels 19 Pages: 107-110
  • NAID: 110002709591
• [Journal Article] Analysis of hematopoietic progenitors in bone marrow from patients with peripheral artery disease (2004)
  • Author(s): Muroi K, Ikeda U, et al.
  • Journal Title: Leuk Res 28 Pages: 28-28
• [Journal Article] Effective hepatocyte transplantation using rat hepatocytes with low asialoglycoprotein receptor expression. (2004)
  • Author(s): Ise H, Ikeda U, et al.
  • Journal Title: Am J Pathol 165 Pages: 501-510
• [Journal Article] Adeno-associated Virus vector-mediated lnterleukin-10 gene transfer inhibits atherosclerosis in apolipoprotein E-deficient mice. (2004)
  • Author(s): Yoshioka T, Ikeda U, et al.
  • Journal Title: Gene Ther 11 Pages: 1772-1779
• [Journal Article] Cardiac function-related gene expression profiles in human atrial myocytes. (2004)
  • Author(s): Ohki-Kaneda, Ikeda U, et al.
  • Journal Title: Biochem Biophys Res Commun 320 Pages: 1328-1336
• [Book] Annual Review循環器科(虚血肢に対する末梢幹細胞移植) (2006)
  • Author(s): 鈴木智裕, 高橋将文, 吉岡徹, 池田宇一
  • Publisher: 中外医学社
  • Description: 「研究成果報告書概要(和文)」より
• [Book] Annual Review循環器科 (2006)
  • Author(s): 鈴木智裕, 高橋将文, 吉岡徹, 池田宇一
  • Publisher: 中外医学社
• [Book] Annual Review循環器科 (2004)
  • Author(s): 松井圭司, 高橋将文, 池田宇一
  • Publisher: 中外医学社