| Project/Area Number |
10470279
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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 | TOKYO WOMEN'S MEDICAL UNIVERSITY |
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Principal Investigator |
IMAI Yasuharu TOKYO WOMEN'S MEDICAL UNIVERSITY, Professor, 医学部, 教授 (30075246)
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| Co-Investigator(Kenkyū-buntansha) |
ANDO Makoto TOKYO WOMEN'S MEDICAL UNIVERSITY, Assistant Professor, 医学部, 助手 (70256569)
青木 満 東京女子医科大学, 医学部, 講師 (80175736)
TAKANASHI Yoshinori TOKYO WOMEN'S MEDICAL UNIVERSITY, Professor, 医学部, 教授 (70075505)
MATUOKA Rumiko TOKYO WOMEN'S MEDICAL UNIVERSITY, Assistant Professor, 医学部, 助手 (50120051)
SHINOKA Toshiharu TOKYO WOMEN'S MEDICAL UNIVERSITY, Associate Professor, 医学部, 講師 (20192122)
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥11,700,000 (Direct Cost: ¥11,700,000)
Fiscal Year 2000: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1999: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1998: ¥7,700,000 (Direct Cost: ¥7,700,000)
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| Keywords | Tissue Engineering / blood vessel / heart valve / cell culture / autologous cells / auto-transplantation / 再生血管 / ティッシュエンジニアリング / 生分解ポリマー / 人工血管 / 内皮化 / 自己細胞 / 細胞移植 / 生分解性ポリマー / 心臓外科 / 生体材料 |
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| Research Abstract |
Various vascular grafts are commonly used in the reconstruction of cardiovascular tissues. However, currently used prosthetic or bioprosthetic materials lack growth potential and, therefore, subsequently require replacement in pediatric patients as they mature. Tissue engineering (TE) is a new discipline that offers the potential to create replacement structures from autologous cells and biodegradable polymer scaffolds. Because TE constructs contain living cells, they may have the potential to grow, self-repair, and self-remodel. Tissue Engineered Vascular Autografts (TEVAs) were made by seeding 4-6 x 10^6 of mixed cells obtained from femoral veins of mongrel dogs onto tube-shaped biodegradable polymer scaffolds composed of a polyglycolic acid (PGA) non-woven fabric sheet and a co-polymer of l-lactide and- caprolactone (N=4). After 7 days. the inferior vena cavas (IVCs) of the same dogs were replaced with TEVAs. After 3, 4, 5 and 6 months, angiographies were performed. and the dogs wer
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e sacrificed. The implanted TEVAs were examined both grossly and immunohistologically. The implanted TEVAs showed no evidence of stenosis or dilatation. No thrombus was found inside the TEVAs, even without any anticoagulation therapy. Remnants of the polymer scaffolds were not observed in all specimens, and the overall gross appearance appeared similar to that of native IVCs. Immunohistological staining revealed the presence of Factor VIII positive nucleated cells at the luminal surface of the TEVAs. In addition, lesions were observed where α-smooth muscle actin and desmin positive cells existed. Implanted TEVAs contained a sufficient amount of extracellular matrix, and showed neither occlusion nor aneurysmal formation. In addition, endothelial cells were found to line the luminal surface of each TEVA.These results strongly suggest that 'ideal' venous grafts with anti-thrombogenicity can be produced. Using the TE technique. a peripheral pulmonary artery was successfully reconstructed in a 4-year-old girl using autologous venous cells. The occluded pulmonary artery was reconstructed with the TE vessel graft. No postoperative complications occurred. On follow-up angiography, the transplanted vessels was noted to be completely patent. Long-term follow up is obviously necessary to confirm the feasibility of this approach. However. given our success, we now plan to continue to use this TE technique with autologous cells in only low pressure vessels, such as the venous or pulmonary circulation. Because both our laboratory and clinical experiences are quite encouraging, we suggest that the TE approach may play an important role as an alternative method to transplantation and to the use of artificial organs in the field of pediatric cardiovascular surgery. Less
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