Cell transplantation improves ventricular function in chronic heart failure

• Project/Area Number: 16590710
• 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: Osaka City University
• Principal Investigator: YOSHIYAMA Minoru Osaka City University, Graduate School of Medicine, associate professor, 大学院・医学研究科, 助教授 (30240956)
• Co-Investigator(Kenkyū-buntansha): OMURA Takashi Osaka City University, Graduate School of Medicine, research associate, 大学院・医学研究科, 助手 (70295707) ; TAKEUCHI Kazuhide Osaka City University, Graduate School of Medicine, professor, 大学院・医学研究科, 教授 (80117952) ; 吉川 純一 大阪市立大学, 大学院・医学研究科, 教授 (60275245)
• Project Period (FY): 2004 – 2005
• Project Status: Completed (Fiscal Year 2005)
• Budget Amount: ¥3,600,000 (Direct Cost: ¥3,600,000); Fiscal Year 2005: ¥1,000,000 (Direct Cost: ¥1,000,000); Fiscal Year 2004: ¥2,600,000 (Direct Cost: ¥2,600,000)
• Keywords: Stem cell / myocardial infarction / heart failure / 骨格筋芽細胞 / Myocatrdial infarction / Remodeling / Cell therapy / Stem cell / Signal transduction / Echocardiography

Research Abstract

Cell transplantation, offers the promise in the restoration of ventricular function after an extensive myocardial infarction, but the optimal cell therapy remains controversial. Vascular endothelial growth factor (VEGF) plays an important role in inducing angiogenesis. Mesenchymal stem cells (MSCs) may have potential for differentiation to several types of cells, including myocytes. We hypothesized that transplantation of VEGF-expressing MSCs could effectively treat acute myocardial infarction (MI) by providing enhanced cardioprotection, followed by angiogenic effects in salvaging ischemic myocardium. The human VEGF165 gene was transfected to cultured MSCs of Lewis rats using an adenoviral vector. Six million VEGF-transfected and LacZ-transfected MSCs (VEGF group), LacZ-transfected MSCs (control group), or serum-free medium only (medium group) were injected into syngeneic rat hearts 1 hour after left coronary artery occlusion. At 28 days after MI, infarct size, left ventricular dimensions, ejection fraction, E wave/A wave ratio and capillary density of the infarcted region were most improved in the VEGF group, compared with the medium group. Immunohistochemically, alpha-smooth muscle actin-positive cells were most increased in the VEGF group. This combined strategy of cell transplantation with gene therapy could be a useful therapy for the treatment of acute MI.

Research Products

• [Journal Article] Microbubbl edestruction with ultrasound augments neovascularisation by bone marrow cell transplantation in rat hind limb ischaemia. (2006)
  • Author(s): Enomoto S, Yoshiyama M, Omura T, Matsumoto R, Kusuyama T, Nishiya D, Izumi Y, Akioka K, Iwao H, Takeuchi K, Yoshikawa J.
  • Journal Title: Heart. 92(4) Pages: 515-520
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Involvement of c-Jun NH2 terminal kinase and p38MAPK in rapamycin-mediated inhibition of neointimal formation in rat carotid arteries (2005)
  • Author(s): Omura T, Yoshiyama M, Izumi Y, Kim S, Matsumoto R, Enomoto S, Kusuyama T, Nishiya D, Nakamura Y, Akioka K, Iwao H, Takeuchi K, Yoshikawa J.
  • Journal Title: J Cardiovasc Pharmacol 46(4) Pages: 513-525
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Left ventricular remodeling after myocardial infarction in antecedent hypertensive patients. (2005)
  • Author(s): Yoshiyam M, Kamimori K, Shimada Y, Omura T, Kino N, Iida H, Yoshikawa J.
  • Journal Title: Hypertens Res 28(4) Pages: 293-299
  • NAID: 10016624521
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Angiotensin converting enzyme inhibitor prevents left ventricular remodeling after myocardial infarction in angiotensin II type 1 receptor knockout mice. (2005)
  • Author(s): Yoshiyama M, Nakamura Y, Omura T, Izumi Y, Matsumoto R, Oda S, Takeuchi K, Kim S, Iwao H, Yoshikawa J.
  • Journal Title: Heart 91(8) Pages: 1080-1085
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Angiotensin blockade inhibits osteopontin expression in non-infarcted myocardium after myocardial infarction. (2005)
  • Author(s): Kusuyama T, Yoshiyama M, Omura T, Nishiya D, Enomoto S, Matsumoto R, Izumi Y, Akioka K, Takeuchi K, Iwao H, Yoshikawa J.
  • Journal Title: J Pharmacol Sci. 98(3) Pages: 283-289
  • NAID: 10025729037
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Involvement of c-Jun NH2 terminal kinase and p38MAPK in rapamycin-mediated inhibition of neointimal formation in rat carotid arteries. (2005)
  • Author(s): Omura T, Yoshiyama M, Izumi Y, Kim S, Matsumoto R, Enomoto S, Kusuyama T, Nishiya D, Nakamura Y, Akioka K, Iwao H, Takeuchi K, Yoshikawa J
  • Journal Title: J Cardiovasc Pharmacol. 46(4) Pages: 513-525
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Left ventricular remodeling after myocardial infarction in antecedent hypertensive patients. (2005)
  • Author(s): Yoshiyam M, Kamimori K, Shimada Y, Omura T, Kino N, Iida H, Yoshikawa J
  • Journal Title: Hypertens Res. 28(4) Pages: 293-299
  • NAID: 10016624521
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Angiotensin converting enzyme inhibitor prevents left ventricular remodeling after myocardial infarction in angiotensin II type 1 receptor knockout mice. (2005)
  • Author(s): Yoshiyama M, Nakamura Y, Omura T, Izumi Y, Matsumoto R, Oda S, Takeuchi K, Kim S, Iwao H, Yoshikawa J
  • Journal Title: Heart. 91(8) Pages: 1080-1085
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Angiotensin blockade inhibits osteopontin expression in non-infarcted myocardium after myocardial infarction. (2005)
  • Author(s): Kusuyama T, Yoshiyama M, Omura T, Nishiya D, Enomoto S, Matsumoto R, Izumi Y, Akioka K, Takeuchi K, Iwao H, Yoshikawa J
  • Journal Title: J Pharmacol Sci. 98(3) Pages: 283-289
  • NAID: 10025729037
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Microbubble destruction with ultrasound augments neovascularisation by bone marrow cell transplantation in rat hind limb ischaemia. (2005)
  • Author(s): Enomoto S, Yoshiyama M, Omura T, Matsumoto R, Kusuyama T, Nishiya D, Izumi Y, Akioka K, Iwao H, Takeuchi K, Yoshikawa J
  • Journal Title: Heart. 92(4) Pages: 515-520
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Involvement of c-Jun NH2 terminal kinase and p38MAPK in rapamycin-mediated inhibition of neointimal formation in rat carotid arteries (2005)
  • Author(s): Omura T, Yoshiyama M, Izumi Y, Kim S, Matsumoto R, Enomoto S, Kusuyama T, Nishiya D, Nakamura Y, Akioka K, Iwao H, Takeuchi K, Yoshikawa J
  • Journal Title: J Cardiovasc Pharmacol 46(4) Pages: 513-525
• [Journal Article] Left ventricular remodeling after myocardial infarction in antecedent hypertensive patients. (2005)
  • Author(s): Yoshiyama M, Kamimori K, Shimada Y, Omura T, Kino N, Iida H, Yoshikawa J.
  • Journal Title: Hypertens Res 28(4) Pages: 293-299
  • NAID: 10016624521
• [Journal Article] Core Protein of Hepatitis C Virus Induces Cardiomyopathy. (2005)
  • Author(s): Omura T, Yoshiyama M, Hayashi T, Iwao H, Yoshikawa J et al.
  • Journal Title: Circ Res. 96 Pages: 148-150
• [Journal Article] Involvement of apoptosis signal-regulating kinase-1 on angiotensin II-induced monocyte chemoattractant protein-1 expression. (2004)
  • Author(s): Omura T, Yoshiyama M, Akioka K, Takeuchi K, Yoshikawa J et al.
  • Journal Title: Arterioscler Thromb Vasc Biol. 24 Pages: 270-275
• [Journal Article] Effects of cellular cardiomyoplasty on ventricular remodeling assessed by Doppler echocardiography and topographic immunohistochemistry. (2004)
  • Author(s): Yoshiyama M, Hayashi T, Nakamura Y, Omura T, Yoshikawa J et al.
  • Journal Title: Circ J. 68 Pages: 580-586
  • NAID: 110002692160
• [Journal Article] Cardioprotective effect of SEA0400,a selective inhibitor of the Na(+)/Ca(2+) exchanger, on myocardial ischemia-reperfusion injury in rats. (2004)
  • Author(s): Yoshiyama M, Nakamura Y, Omura T, Iwao H, Yoshikawa J et al.
  • Journal Title: J Pharmacol Sci. 95 Pages: 196-202
  • NAID: 10013294783
• [Journal Article] Effects of aldosterone receptor antagonist and angiotensin II type I receptor blocker on cardiac transcriptional factors and mRNA expression in rats〜〜. (2004)
  • Author(s): Matsumoto R, Yoshiyama M, Omura T, Kim S, Akioka K et al.
  • Journal Title: Circ J. 68 Pages: 376-382
• [Journal Article] Additive improvement of left ventricular remodeling by aldosterone receptor blockade with eplerenone and angiotensin II type 1 receptor antagonist〜〜. (2004)
  • Author(s): Yoshiyama M, Omura T, Yoshikawa J..
  • Journal Title: Nippon Yakurigaku Zasshi. 124(2) Pages: 83-89