| Project/Area Number |
14370422
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Thoracic surgery
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| Research Institution | National Cardiovascular Center Research Institute |
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Principal Investigator |
TAKEWA Yoshiaki National Cardiovascular Center Research Institute, Artificial Organs, Laboratory Chief, 人工臓器部, 室長 (20332405)
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| Co-Investigator(Kenkyū-buntansha) |
TAKANO Hisateru National Cardiovascular Center Research Institute, Research Institute, Deputy Director, 副所長 (60028595)
TAENAKA Yoshiyuki National Cardiovascular Center Research Institute, Artificial Organs, Director, 人工臓器部, 部長 (00142183)
TATSUMI Eisuke National Cardiovascular Center Research Institute, Artificial Organs, Laboratory Chief, 人工臓器部, 室長 (00216996)
HOMMA Akihiko National Cardiovascular Center Research Institute, Artificial Organs, Research Staff, 人工臓器部, 室員 (20287428)
西中 知博 国立循環器病センター研究所, 人工臓器部, 室長 (00256570)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥11,600,000 (Direct Cost: ¥11,600,000)
Fiscal Year 2004: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2003: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2002: ¥4,300,000 (Direct Cost: ¥4,300,000)
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| Keywords | Ventricular assist device / Mechanical assist circulation / Regeneration therapy / Hepatocyto growth factor / Myocardial infarction / Left ventricular remodeling / Refractory heart failure / Gene transfection / 左室リモデリング |
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| Research Abstract |
The purpose of this study is to evaluate the usefulness of combination therapy between ventricular assist device(VAD) support and cardiac regeneration such as gene therapy or cell transplantation. I started this study when I moved from Nara Medical University to National Cardiovascular Center Research Institute.
First, we examined a gene therapy for angiogenesis to acute myocardial infarction in goats under ventricular assist system(VAS). Six adult goats (56-65kg) were created the impaired heart by ligating the coronary artery and installed pulsatile bi-VADs. Hepatocyte Growth Factor(HGF) was selected as a gene of an angiogenesis factor, which also has cardioprotective activities. The HGF group (n=3) administered human HGF-cDNA plasmid of 2.0 mg in myocardium. The control group (n=3) administered beta-galactosidase plasmid similarly. Four weeks after gene transfection, all goats were tried to wean from VADs. The myocardia transfected with the hHGF-cDNA contained hHGF protein at levels a
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s high as 1.0+/-0.3 ng/g tissue 3 days after transfection. After weaning from VADs, the HGF group showed good hemodynamics while the control group showed its deterioration. The percent fractional shortening was significantly higher in the HGF group than the control group (HGF vs.control,37.9+/-1.7% vs.26.4+/-0.3%, p<0.01). LV dilatation associated with myocytes hypertorcphy and fibrotic changes were detected in the control group while not in the HGF group. Vascular density was markedly increased in the HGF group. These results suggest that gene therapy using hHGF may enhance the chance of "bridge to recovery" in the impaired heart under VAS.
Second, we examined a cell transplantation to cardiomyopathy in goats supported with left VAD(LVAD). Four adult goats weighing 55.7+/-3.2 kg were created heart failure by infusing adriamycin for 5 weeks. All goats were instaled a pulsatile LVAD and maintained systmic circulation sufficiently. Two of 4 goats were infused autologus bone marrow-derived stromal cells(BMSC) which were previously cultured in vitro(BMSC group), and the rest 2 goats were not infused them (control group). All goats were continued LVAD support for 4 weeks, and cardiac function and hemodynamics were serially recorded. The BMSC group recovered better cardiac function (the LV Ejection Fraction (EF) ; from 39.3+/-2.3% to 47.0+/-14.0%) than the control group did (EF ; from 32.6+/-0.7% to 26.0+/-4.3%). Wall thinning of the myocardium was more suppressed in the BMSC group than that in the control group.
In conclusion, additional regeneration therapy to severe failing heart supported with LVAD may contribute to recover cardiac function and increase the possibility of bridge to recovery. Less
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