| Project/Area Number |
15086201
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Science and Engineering
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| Research Institution | Hokkaido University |
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Principal Investigator |
KARINO Takeshi Hokkaido University, Research Institute for Electronic Science, Prof. (30241384)
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| Co-Investigator(Kenkyū-buntansha) |
NIWA Kouichi Tokyo Univ of Agriculture, Fac. of Bioindustry, Assoc. Prof (20301012)
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| Project Period (FY) |
2003 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥32,500,000 (Direct Cost: ¥32,500,000)
Fiscal Year 2006: ¥8,200,000 (Direct Cost: ¥8,200,000)
Fiscal Year 2005: ¥8,700,000 (Direct Cost: ¥8,700,000)
Fiscal Year 2004: ¥8,400,000 (Direct Cost: ¥8,400,000)
Fiscal Year 2003: ¥7,200,000 (Direct Cost: ¥7,200,000)
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| Keywords | hybrid vascular graft / intimal hyperplasia / flow velocity / disturbed flow / shear stress / endothelial cell / smooth muscle cell / water filtration / 動脈硬化 / 単核細胞 / 体外循環 / 組織工学 / 灌流圧 / LDL濃度 / 組織構造 |
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| Research Abstract |
One of the big problems in vascular reconstructive surgery of occluded arteries with autologus vein and artificial grafts is re-occlusion of the grafts by the formation of mural thrombi and development of intimal hyperplasia. It is especially serious with small caliber synthetic grafts. Thus, no artificial graft smaller than 6-mm diameter is used clinically at present. It is awaited to develop a small caliber vascular graft that is free from the formation of mural thrombi and intimal hyperplasia. To solve the problem, we devised a new and simple method to prepare small caliber hybrid vascular grafts by pressure seeding bovine aortic smooth muscle cells and endothelial cells in suspensions on the luminal surface of a 3.0-mm diameter water-permeable ePTFE graft and co-cultivating them. Then using it, we studied the effects of various physical and fluid mechanical factors on proliferation of the cells of the hybrid graft. It was found that slow flows that imposed low wall shear stresses on endothelial cells and water filtration promoted the growth and proliferation of smooth muscle cells underlying the endothelial cells. It was also found that in regions of a disturbed flow caused by the formation of a vortex, adhesion of monocytes and polystyrene microspheres used as a model of LDL to the endothelial cells was enhanced at the stagnation and reattachment points where flow was slow and wall shear stress was low, and the thickness of the cell layer was much greater. These results well agree with clinical findings that intimal hyperplasia develop preferentially in regions of slow flow (low wall shear stress), indicating that the cells of the hybrid graft bears the same character as those of natural arteries in vivo. Thus the hybrid grafts we developed could be used as a substitute for an artery in various in vitro flow experiments.
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