Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2002: ¥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 Autografts (TEAs) were made by seeding 4-6 x 10^6 of mixed cells obtained from femoral veins of mongrel dogs onto valved patch-shape 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 pulmonary valve leaflet of the same dogs was replaced with TEAs. After 3, 4, 5 and 6 months, angiographies were performed, and the dogs were sacrif
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iced. The implanted TAs were examined both grossly and immunohistologically. The implanted TEAs showed no evidence of stenosis or dilatation. No thrombus was found inside the TEAs, 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 pulmonary valves. Immunohistological staining revealed the presence of Factor VIII positive nucleated cells at the luminal surface of the TEAs. In addition, lesions were observed where α-smooth muscle actin and desmin positive cells existed. Implanted TEAs 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 TEA. These results strongly suggest that 'ideal' grafts with anti-thrombogenicity can be produced. 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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