Sono-cell therapy to coronary artery disease and heart failure

• Project/Area Number: 14370233
• 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: Osaka City University
• Principal Investigator: OMURA Takashi (2005) Osaka City University, Graduate School of Medicine, research associate, 大学院・医学研究科, 助手 (70295707); 吉川 純一 (2002-2004) 大阪市立大学, 大学院・医学研究科, 教授 (60275245)
• Co-Investigator(Kenkyū-buntansha): YOSHIYAMA Minoru Osaka City University, Graduate School of Medicine, associate professor, 大学院・医学研究科, 助教授 (30240956) ; 大村 崇 大阪市立大学, 大学院・医学研究科, 助手 (70295707)
• Project Period (FY): 2002 – 2005
• Project Status: Completed (Fiscal Year 2005)
• Budget Amount: ¥13,800,000 (Direct Cost: ¥13,800,000); Fiscal Year 2005: ¥3,400,000 (Direct Cost: ¥3,400,000); Fiscal Year 2004: ¥3,400,000 (Direct Cost: ¥3,400,000); Fiscal Year 2003: ¥3,400,000 (Direct Cost: ¥3,400,000); Fiscal Year 2002: ¥3,600,000 (Direct Cost: ¥3,600,000)
• Keywords: Stem cell / sono-therapy / myocardial infarction / heart failure / 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 showed 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. Moreover, to examine the effects of microbubble destruction with ultrasound (MB) combined with bone marrow derived mononuclear cell transplantation (BMT) into ischaemic tissues in rat hind limb ischaemia. MB treatment increased vascular endothelial growth factor mRNA as assessed by real time polymerase chain reaction. At four weeks, the MB group had increases in laser Doppler blood flow index, angiographically detectable collateral vessels, and capillary to muscle fiber ratio in ischaemic limbs compared with the vehicle treated group. Secondly, rats were allocated to vehicle treatment, BMT (5×10(6) cells/rat), or a combination of MB and BMT (MB+BMT) at seven days after hind limb ischaemia. BMT treatment significantly increased LDBFI, angiographic score, and capillary to muscle fiber ratio compared with vehicle treatment. MB may be a useful technique to enhance BMT induced neovascularisation and improve the effect of cell therapy.

Research Products

• [Journal Article] Prevalence and clinical course of the juveniles with Brugada-type ECG in Japanese population. (2006)
  • Author(s): Oe H, Takagi M, Tanaka A, Namba M, Nishibori Y, Nishida Y, Kawarabayashi T, Yoshiyama M, Nishimoto M, Tanaka K, Yoshikawa J.
  • Journal Title: Pacing Clin Electrophysiol. 28(6) Pages: 549-554
  • 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): Fukuda D, Yoshiyama M, Shimada K, Yamashita H, Ehara S, Nakamura Y, Kamimori K, Tanaka A, Kawarabayashi T, Yoshikawa J.
  • Journal Title: Heart. 10
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Impaired coronary circulation in patients with apical hypertrophic (2005)
  • Author(s): Yoshida K, Hozumi T, Takemoto Y, Sugioka K, Watanabe H, Muro T, Yoshiyama M, Takeuchi K, Yoshikawa J.
  • Journal Title: Echocardiography 22(9) Pages: 723-729
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Relation between reduction in ischaemic mitral regurgitation and improvement in regional left ventricular contractility during low dose dobutamine stress echocardiography. (2005)
  • Author(s): Abe Y, Imai T, Ohue K, Otsuka R, Komatsu R, Otsuka M, Sakanoue Y, Naruko T, Itoh A, Yoshiyama M, Haze K, Yoshikawa J.
  • Journal Title: Heart 91(8) Pages: 92-1093
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] A novel technique to detect total occlusion in the right coronary artery using retrograde flowby transthoracic Doppler echocardiography. (2005)
  • Author(s): Otsuka R, Watanabe H, Hirata K, Tokai K, Muro T, Hozumi T, Yoshiyama M, Yoshikawa J.
  • Journal Title: J Am Soc Echocardiogr. 18(7) Pages: 704-709
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Impaired coronary circulation in patients with apical hypertrophic. (2005)
  • Author(s): Yoshida K, Hozumi T, Takemoto Y, Sugioka K, Watanabe H, Muro T, Yoshiyama M, Takeuchi K, Yoshikawa J.
  • Journal Title: Echocardiography. 22(9) Pages: 723-729
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Relation between reduction in ischaemic mitral regurgitation and improvement in regional left ventricular contractility during low dose dobutamine stress echocardiography. (2005)
  • Author(s): Abe Y, Imai T, Ohue K, Otsuka R, Komatsu R, Otsuka M, Sakanoue Y, Naruko T, Itoh A, Yoshiyama M, Haze K, Yoshikawa J.
  • Journal Title: Heart. 91(8) Pages: 1092-1093
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] A novel technique to detect total occlusion in the right coronary artery using retrograde flow by transthoracic Doppler echocardiography. (2005)
  • Author(s): Otsuka R, Watanabe H, Hirata K, Tokai K, Muro T, Hozumi T, Yoshiyama M, Yoshikawa J.
  • Journal Title: J Am Soc Echocardiogr. 18(7) Pages: 704-709
  • 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): Fukuda D, Yoshiyama M, Shimada K, Yamashita H, Ehara S, Nakamura Y, Kamimori K, Tanaka A, Kawarabayashi T, Yoshikawa J.
  • Journal Title: Heart. 10
• [Journal Article] Relation between reduction in ischaemic mitral regurgitation and improvement in regional left ventricular contractility during low dose dobutamine stress echocardiography. (2005)
  • Author(s): Abe Y, Imai T, Ohue K, Otsuka R, Komatsu R, Otsuka M, Sakanoue Y, Naruka T, Itoh A, Yoshiyama M, Haze K, Yoshikawa J.
  • Journal Title: Heart 91(8) Pages: 1092-1093
• [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 Vase 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
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