| Co-Investigator(Kenkyū-buntansha) |
AOKI Mitsuru TOKYO WOMEN'S MEDICAL UNIVERSITY, Associate Professor, 医学部, 講師 (80175736)
SHINOKA Toshiharu TOKYO WOMEN'S MEDICAL UNIVERSITY, Associate Professor, 医学部, 講師 (20192122)
SEO Kazuhiro TOKYO WOMEN'S MEDICAL UNIVERSITY, Associate Professor, 医学部, 講師 (20167472)
今井 康晴 東京女子医科大学, 医学部, 教授 (30075246)
寺田 正次 東京女子医科大学, 医学部, 講師 (90172098)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
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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 1-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 we
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re 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. Immundhistological 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 were noted to be completely patent. In the same manner, autologous pericardium using biodegradable polymer sheet was examined in an animal model. Pericardial adhesion was relatively mild comparing to the prosthetic materials. 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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