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Stem Cell Transplantation Attenuates Deleterious Ventricular Remodeling and Improves Cardiac Performance After Myocardial Infarction

Research Project

Project/Area Number 13670738
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionOsaka City University

Principal Investigator

TAKEUCHI Kazuhide  Osaka City University, Graduate School of Medicine, Professor, 大学院・医学研究科, 教授 (80117952)

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)
YOSHIKAWA Junichi  Osaka City University, Graduate School of Medicine, Professor, 大学院・医学研究科, 教授 (60275245)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2001: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsMyocardial infarction / Remodeling / Cell therapy / Stem Cell / Heart failure / Signal transduction / Myocardial infarction / Stemcell / 心臓リモデリング / 再生医学 / 冠動脈リモデリング
Research Abstract

Myocardial infarction (MI) promotes deleterious remodeling of the myocardium, resulting in ventricular dilation and pump dysfunction. We examined whether supplementing infarcted myocardium with stem cell would attenuate deleterious remodeling, and enhance contractile performance. Experimental MI was induced by 24-hours coronary ligation followed by reperfusion in adult male Lewis rats and neonatal myocytes were injected directly into the infarct region. Three groups of animals were studied at 4 weeks after cell therapy: noninfarcted control (control), MI plus sham injection (MI), and MI plus stem cell injection (MI+cell). In vivo cardiac function was assessed by echocardiography. MI and MI+cell hearts had indistinguishable infarct sizes of 30% of the LV. At 4 weeks after cell therapy, 92% (13 of 14) of MI+cell hearts showed evidence of myocytes graft survival. MI+cell hearts exhibited attenuation of global ventricular dilation and reduced septum and free wall diameter compared with MI hearts not receiving cell therapy. Implanted stem cell form viable grafts in infarcted myocardium, resulting in enhanced contractile function and attenuated ventricular dilation. These data illustrate that stem cell implantation after MI improves both in systolic and diastolic dysfunction and deleterious remodeling and suggests that cellular implantation may be beneficial after MI.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (25 results)

All Other

All Publications (25 results)

  • [Publications] Nakamura Y, Yoshiyama M, Omura T, Yoshida K, Izumi Y, Takeuchi K, Kim S, Iwao H, Yoshikawa J.: "Beneficial effects of combination of ACE inhibitor and angiotensin II type 1 receptor blocker on cardiac remodeling in rat myocardial infarction"Cardiovascular Research. 57. 48 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Omura T, Yoshiyama M, Yoshida K, Nakamura Y, Kim S, Iwao H, Takeuchi K, Yoshikawa J: "Dominant negative mutant of c-Jun inhibits cardiomyocyte hypertrophy induced by endothelin 1 and phenylephrine"Hypertension. 39. 81 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakamura Y, Yoshiyama M, Omura T, Yoshida K, Kim S, Takeuchi K, Iwao H, Yoshikawa J: "Transmitral inflow pattern assessed by Doppler echocardiography in angiotensin II type 1A receptor knockout mice with myocardial infarction"Circulation Journal. 66. 192 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Izutani S, Yoshiyama M, Omura T, Yoshida K, Nakamura Y, Kim S, Takeuchi K, Yoshikawa J: "Niporadilol can prevent left ventricular systolic and diastolic dysfunction after myocardial infarction in rats"Circulation Journal. 66. 289 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Omura T, Yoshiyama M, Ishikura F, Kobayashi H, Takeuchi K, Beppu S, Yoshikawa J: "Myocardial ischemia activates the JAK-STAT pathway through angiotensin II signaling in vivo myocardium of rats"Journal of Molecular and Cellular Cardiology. 33. 307 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshiyama M, Omura T, Takeuchi K, Kim S, Yamagishi H, Akioka K, Iwao H, Yoshikawa J: "Angiotensin blockade inhibits increased JNKs, AP-1 and NF-kappa B DNA-binding activities in myocardial infarcted rats"Journal of Molecular and Cellular Cardiology. 33. 799 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakamura Y, Yoshiyama M, Omura T, Yoshida K, Kim S, Takeuchi K, Iwao H, Yoshikawa J.: "Transmitral inflow pattern assessed by Doppler echocardiography in angiotensin II type 1A receptor knockout mice with myocardial infarction."Circ J.. 66. 192-196 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shirai N, Yamagishi H, Yoshiyama M, Teragaki M, Akioka K, Takeuchi K, Yoshikawa J, Ochi H.: "Incremental value of assessment of regional wall motion for detection of multivessel coronary artery disease in exercise (201)T1 gated myocardial perfusion imaging."J Nucl Med.. 43. 443-450 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Izutani S, Yoshiyama M, Omura T, Yoshida K, Nakamura Y, Kim S, Takeuchi K, Yoshikawa J.: "Nipradilol can prevent left ventricular systolic and diastolic dysfunction after myocardial infarction in rats."Circ J.. 66. 289-293 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ehara S, Ueda M, Naruko T, Haze K, Matsuo T, Ogami M, Ikura Y, Itabe H, Komatsu R, Yoshiyama M, Takeuchi K, Yoshikawa J.: "Pathophysiological role of oxidized low-density lipoprotein in plaque instability in coronary artery diseases."J Diabetes Complications.. 16. 60-64 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamagishi H, Shirai N, Yoshiyama M, Teragaki M, Akioka K, Takeuchi K, Yoshikawa J, Ochi H.: "Incremental value of left ventricular ejection fraction for detection of multivessel coronary artery disease in exercise (201)T1 gated myocardial perfusion imaging."J Nucl Med.. 43. 131-139 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Omura T, Yoshiyama M, Yoshida K, Nakamura Y, Kim S, Iwao H, Takeuchi K, Yoshikawa J.: "Dominant negative mutant of c-Jun inhibits cardiomyocyte hypertrophy induced by endothelin 1 and phenylephrine."Hypertension.. 39. 81-86 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakamura Y, Yoshiyama M, Omura T, Yoshida K, Izumi Y, Takeuchi K, Kim S, Iwao H, Yoshikawa J.: "Beneficial effects of combination of ACE inhibitor and angiotensin II type 1 receptor blocker on cardiac remodeling in rat myocardial infarction."Cardiovasc Res.. 57. 48-54 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakamura Y, Yoshiyama M, Omura T, Yoshida K, Izumi Y, Takeuchi K, Kim S, Iwao H, Yoshikkawa J: "Beneficial effects of combination of ACE inhibitor and angiotensin II type 1 receptor blocker on cardiac remodeling in rat myocardial infarction"Cardiovascular Research. 57. 48 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Omura T, Yoshiyama M, Yoshida K, Nakamura Y, Kim S, Iwao H, Takeuchi K, Yoshikawa J: "Dominant negative mutant of c-Jun inhibits cardiomyocyte hypertrophy induced by endothelin 1 and phenylephrine"Hypertension. 39. 81 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nakamura Y, Yoshiyama M, Omura T, Yoshida K, Kim S, Takeuchi K, Iwao H, Yoshikawa J: "Transmitral inflow pattern assessed by Doppler echocardiography in angiotensin II type 1A receptor knockout mice with myocardial infarction"Circulation Journal. 66. 192 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Izutani S, Yoshiyama M, Omura T, Yoshida K, Nakamura Y, Kim S, Takeuchi K, Yoshikawa J: "Nipradilol can prevent left ventricular systolic and diastolic dysfunction after myocardial infarction in rats"Circulation Journal. 66. 289 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Omura T, Yoshiyama M, Ishikura F, Kobayashi H, Takeuchi K, Beppu S, Yoshikawa J: "Myocardial ischemia activates the JAK-STAT pathway through angiotensin II signaling in in vivo myocardium of rats"Journal of Molecular and Cellular Cardiology. 33. 307 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yoshiyama M, Omura T, Takeuchi K, Kim S, Yamagishi H, Akioka K, Iwao H, Yoshikawa J: "Angiotensin blockade inhibits increased JNKs, AP-1 and NF-kappa B DNA-binding activities in myocardial infarcted rats"Journal of Molecular and Cellular Cardiology. 33. 799 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] 山岸広幸, 秋岡要, 葭山稔, 竹山一秀 et al.: "Dobutamine stress electrocardiography-gated Tc-99m tetrofosmin SPECT for detection of viable but dysfunctional myocardium"J Nucl Cardiol. 8. 58-67 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 平田久美子, 葭山稔, 竹内一秀, 吉川純一 et al.: "Modulation of coronary flow velocity reserve by gender, menstrual cycle and hormone replacement therapy"J Am Coll Cardiol. 38. 1879-1884 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 大村崇, 葭山稔, 竹内一秀 et al.: "Myocardial ischemia activates the JAK-STAT pathway through angiotensin II signaling in in vivo mvocardium of rats"J Mol Cell Cardiol. 33. 307-316 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 大塚亮, 渡辺弘文, 竹内一秀, 吉川純一 et al.: "Acute effects of passive smoking on the coronary circulation in healthy young adults"JAMA. 286. 436-441 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 江原省一, 上田真喜子, 竹内一秀, 吉川純一 et al.: "Elevated levels of oxidized low density lipoprotein show a positive relationship with the severity of acute coronary syndromes"Circulation. 103. 1955-1960 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 葭山稔, 大村崇, 竹内一秀 et al.: "Angiotensin blockade inhibits increased JNKs, AP-1 and NF-kappa B DNA-binding activities in myocardial infarcted rats."J Mol Cell Cardiol. 33. 799-810 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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