2002 Fiscal Year Final Research Report Summary
THE INVESTIGATION OF THE MECHANISM OF PROLIFERATION AND DIFFERERNTIATION AFTER CELL TRANSPLANTATION INTO MYOCARDIUM AND THE DEVELOPMENT OF OPTIMAL TRANSPLANT CELLS
| Project/Area Number |
12671305
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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 |
Thoracic surgery
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| Research Institution | SHIGA UNIVERSITY OF MEDICAL SCIENCE |
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Principal Investigator |
SHIRAISI Shoichiro SHIGA UNIVERSITY OF MEDICAL SCIENCE MEDICINE ASSOCIATE PROFESSOR, 医学部, 助手 (30283568)
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| Project Period (FY) |
2000 – 2002
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| Keywords | cell transplantation / ischemic cardiomyopathy / smooth muscle cells / angiogenesis / left ventricular remodling / extra cellular matrix |
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| Research Abstract |
Methods : Adult Lewis rats underwent LV free wall cryoinjury to create a transmural scar. Aortic smooth muscle cells (ASMCs) and uterine smooth muscle cells (USMCs) of syngeneic rats were cultured to passage 3 prior to transplantation. Three weeks after myocardial injury ASMCs and USMCs (5x10^6) were transplanted into the scar. Transplanted cells were prelabeled with BrdU to facilitate identification following transplantation. After 5 weeks the hearts were excised and Langendorff functional analysis, computerized planimetry and quantitative histologic analysis with NIH image were performed. The angiogenic factors, VEGF and bFGF level in the transplanted scar tissue were evaluated using slot blotting analysis. Results : The VEGF level in the transplanted scar tissue with both ASMCs and USMCs was increased. Both ASMCs and USMCs labeled with BrdU engrafted in the cryoinjured region and formed new more blood vessels than the control. Computerized planimetry demonstrated that ASMCs and USMCs transplantation maintained the engrafted scar thickness and prevented scar expansion. The extra cellular matrix such as elastin and total collagen was reconstructed better in ASMCs transplantation. The hearts transplanted with both ASMCs and USMCs were able to develop higher pressures at any balloon volumes suggesting better function. Conclusions : 1. Smooth muscle cells engrafted in the scar region and induced a profound angiogenesis by a variety of mechanisms including the secretion of angiogenic factors, in addition, improve systolic function. 2. Engrafted cells in the scar lesion survived at least 5 weeks after transplantation. Engrafted smooth muscle cells themselves were suggested to form some parts of new vessels. 3. The engrafted cells prevented scar thinning and expansion. It is indicated that engrafted ASMCs induced extra cellular matrix and associated with the LV remodeling in the scar area.
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