2002 Fiscal Year Final Research Report Summary
Gene Therapy in Combination with Myoblast Transplantation for Global Non-ischemic Failing Hearts.
| Project/Area Number |
13670710
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Kobe University |
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Principal Investigator |
KAWASHIMA Seinosuke Kobe University Graduate School of Medicine, Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (10177678)
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| Co-Investigator(Kenkyū-buntansha) |
YOKOYAMA Mitsuhiro Kobe University Graduate School of Medicine, Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Professor, 大学院・医学系研究科, 教授 (40135794)
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| Project Period (FY) |
2001 – 2002
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| Keywords | cell transpdlantation / heart failure / myoblast / gene therapy / cardiotrophin-1 |
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| Research Abstract |
Skeletal myoblast transplantation can be a candidate for the treatment of heart failure. This strategy is also useful as a tool for cell-mediated gene therapy. In the present study, we examined the effects of autologous myoblast transplantation in non-ischemia-based heart failure. For this purpose, we used Dahl salt-sensitive hypertensive rats (DS rats), which show the transition from compensatory hypertrophied heart (LVH stage) to failed heart (CHF stage). At the LVH stage (11 weeks of age), autologous myoblast transplantation was performed by direct injection to the heart and cardiac function as well as cardiac morphology was examined at CHF stage (17 weeks of age). Transplantation of myoblasts alleviated LV remodeling and worsening of cardiac function. Then we tried to develop a new therapy by combination of gene therapy with myoblast transplantation. Cardiotrophin-1 has been revealed to induce cardiomyocyte hypertrophy and serve as a cardioprotective factor. We transfected CT-1 gene to myoblasts by retrovirus and then those CT-1-expressing myoblasts were transplanted to the hearts of DS rats. The transplantation of CT-1-expressing myoblasts augmented the beneficial effects of cell transplantation ; LV remodeling was more prevented and cardiac function was more preserved compared to myoblast transplantation alone. Histological examination revealed an increase of size of cardiomyocytes adjacent to the transplanted myoblasts. Further, activation of endothelin system, which contributes to the transition to heart failure, was prevented by CT-1-expressing myoblast transplantation. The present study demonstrated the possibility of autologous myoblasts transplantation for therapy of non-ischemia-based heart failure. Further, the combination of gene therapy using cardioprotective genes such as CT-1 with cell transplantation can be a promising new strategy.
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[Publications] Namiki M, Kawashima S, Yamashita T, Ozaki M, Hirase T, Ishida T, Inoue N, Hirata K, Matsukawa A, Morishita R, Kaneda Y, Yokoyama M.: "Local overexpression of monocyte chemoattractant protein-1 at vessel wall induces infiltration of macrophages and formation of atherosclerotic lesion : synergism with hypercholesterolemia"Arterioscler Thromb Vase Biol. 22(1). 115-120 (2002)
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[Publications] Ozaki M, Kawashima S, Yamashita T, Hirase T, Namiki M, Inoue N, Hirata K, Yasui H, Sakurai H, Yoshida Y, Masada M, Yokoyama M.: "Overexpression of endothelial nitric oxide synthase accelerates atherosclerotic lesion formation in apoE-deficient mice"J Clin Invest. 110(3). 331-340 (2002)
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