• Journal of Chest Surgery
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• v.37 no.6
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• pp.474-481
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• 2004

Background: Tracheal transplantation is necessary in patients with extensive tracheal stenosis, congenital lesions and other oncologic conditions but bears. many critical problems compared to other organ transplantations. The purpose of this study was to develop intestine-cartilage composite grafts for potential application in tracheal reconstruction by free intestinal graft. Material and Method: Hyaline cartilage was harvested from trachea of 2 weeks old New Zealand White Rabbits. Chondrocytes were isolated and cultured for 8 weeks. Cultured chondrocytes were seeded in the PLGA scaffolds and mixed in pluronic gel Chondrocyte bearing scaffolds and gel mixture were embedded in submucosal area of stomach and colon of 3 kg weighted New Zealand White Rabbits under general anesthesia. 10 weeks after implantation, bowels were harvested for evaluation. Result: We identified implantation site by gross examination and palpation. Developed cartilage made a good frame for shape memory. Microscopic examinations included special stain s howed absorption of scaffold and cartilage formation even though it was not fully matured. Conclusion: Intestine-cartilage composite graft could be applicable in the future as tracheal substitute and should be further investigated.

• Journal of Chest Surgery
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• v.46 no.5
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• pp.328-339
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• 2013

Background: Ischemic injury and the rejection process are the main reasons for graft failure in tracheal transplantation models. To enhance the acceptance, we investigated the influence of mesenchymal stem cells (MSCs) on tracheal allografts. Methods: Extracted tracheal grafts from New Zealand white rabbits were cryopreserved for 4 weeks and orthotopically transplanted (control group A, n=8). In group B (n=8), cyclosporin A (CsA, 10 mg/kg) was injected daily into the peritoneal cavity. In group C (n=8), MSCs ($1.0{\times}10^7$ cells/kg) from the same donor of the tracheal allograft, which had been pre-cultured for 4 weeks, were infused intravenously after transplantation. In group D (n=8), MSCs were infused and CsA was injected daily. Four weeks after transplantation, gross and histomorphological assessments were conducted for graft necrosis, measuring the cross-sectional area of the allograft, determining the degree of epithelization, lymphocytic infiltration, and vascular regeneration. Results: The morphologic integrity of the trachea was retained completely in all cases. The cross-sectional areas were decreased significantly in group A (p=0.018) and B (p=0.045). The degree of epithelization was enhanced (p=0.012) and the lymphocytic infiltration was decreased (p=0.048) significantly in group D compared to group A. The degree of vascular regeneration did not differ significantly in any of the groups. There were no significant correlations among epithelization, lymphocytic infiltration, and vascular regeneration. Conclusion: The administration of MSCs with concurrent injections of CsA enhanced and promoted epithelization and prevented lymphocytic infiltration in tracheal allografts, allowing for better acceptance of the allograft.

• Journal of Chest Surgery
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• v.30 no.8
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• pp.739-746
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• 1997

A variety of experiments concerning the development of ideal prosthetic grafts for correcting circumferential tracheal defects have been performed. The requirements for an ideal tracheal prosthesis are impermeability to air, consistency to prevent collapse, and acceptance by the host tissue causing a minimum inflammatory reaction, allowing fibroblastic infiltration and epithelialization. The synthetic material, polyurethane(PU), is known as a biocompatible polymer with an inert component. In this study, the tracheal prosthesis was made from microporous PU(30 micrometer in diameter) coated with gelatin and reinforced with isoplastic rings. This procedure provides the prosthesis with a compression strength. The out side diame er of the prosthesis was 20 mm with a length of 30 mm. The gelatin used in the study was obtained from pig skin and immobilized and cross-linked by irradiation(60 Co gamma ray) to promote host tissue incorporation and render the prosthesis epithelization after implantation. Animal experiments using 10 mongrel dogs were performed to compare three kinds of prosthesis; gelatin coated polyurethane graft, uncoated polyurethane graft, and prosthesisf pericadium complex graft. After 6 weeks of implantation, the epithelialization of implants was seen on the gelatin-coated and prosthesisfpericadium complex grafts. Implanted prosthesis were complicated by airway obstruction due to anastomosis granuloma. Early tracheal stenosis was found in the uncoated graft group. Two kind of anastomosis techniques were tested on the gelatin-coated prosthesis. Everted anastomosis resulted severe granuloma than the inverted anastomosis. In the prosthesislpericadium complex graft, bacteria and inflammation at a anastomotic site was found. Based on these results, gelatin coated porous polyurethane trachea prosthesis is biocompatible and may be useful in clinical application with further investigation.

• Journal of Chest Surgery
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• v.32 no.3
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• pp.215-223
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• 1999

Background: The replacement of the narrowed long-segment trachea with various prosthetic materials or tissue grafts remains a difficult and unsolved surgical problem. Homologous cryopreserved tracheal transplantation has been considered to treat the irreversibly-damaged organs, such as in the lung or heart transplantation and also to overcome the limited supply of donor organs. We examined the morphological changes and the immunosuppressive effects of the cryopreserved trachea after the heterotopic transplantation in the rats. Material and Method: Sixty tracheal segments harvested from 30 donor Wistar rats were heterotopically implanted into the peritoneal cavity of 20 recipient Wistar rats and 40 Sprague Dawley rats. The 60 recipient rats were divided into 6 groups(10 rats/ group). In groups I, II, and III, 30 tracheal segments were implanted immediately after the harvesting and in groups IV, V, and VI, the segments were implanted 28 days after the cryopreservation. Groups I and IV were Wistar syngeneic controls. Groups II and V were Sprague Dawley recipients receiving no immunosuppression and Groups III and VI, were Sprague Dawley recipients receiving immunosuppressive agents. At 28 days all rats were sacrificed and the tracheal segments were evaluated grossly and histologically. Result: Immunosuppression of the tracheal segments had a significant influence on the changes of the tracheal lumen and tracheal epithelial cells, irrespective of the cryopreservation of the trachea(p<0.001). In groups III and VI receiving immunosuppressive agents, the tracheal lumen was patent and the normal epithelial cells were observed, however in the other groups not receiving the immunosuppressive agents, there were almost luminal obliteration by the proliferation of the fibrous tissues and a loss of the epithelial cells, the findings were similar to those in the case of obliterative bronchiolitis after a lung and a heart-lung transplantation. Conclusion: With the appropriate immunosuppressive agents, the lumen and the respiratory epithelium of the transplanted tracheal segment were well preserved, even after the cryopreservation of the tracheal segment, which shows the possibility of the long-term preservation and homologous transplantation of the trachea. But fibroproliferative obliteration of the tracheal lumen and the loss of the normal respiratory epithelial cells, characteristic findings of obliterative bronchiolitis, were observed in the groups without the immunosuppression. This experiment using the rat trachea may be useful in studying the pathogenesis, treatment, and prevention of obliterative bronchiolitis after a lung and a heart-lung transplantation.