Reepithelialized Orthotopic Tracheal Allografts Expand Memory Cytotoxic T Lymphocytes But Show No Evidence of Chronic Rejection

Cleven, Heidi; Genden, Eric M.; Moran, Thomas M.

doi:10.1097/01.tp.0000157119.39395.c3

Cited by 11 publications

(10 citation statements)

References 28 publications

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“…To reduce allograft antigenicity further, the inner surface of the trachea should be remodeled and replaced by the recipient's epithelium [20]. This can prevent chronic rejection even after withdrawal of immunosuppression [41]. If the denuded lining of the tracheal allograft is not promptly covered by the recipient's epithelium, fibroproliferative tissues will enter the tracheal lumen via the membranous part [18] and cause airway obliteration and also cause the rejection process to continue unchecked.…”

Section: Discussionmentioning

confidence: 99%

Influence of Mesenchymal Stem Cells on Cryopreserved Tracheal Allografts in Rabbits

Kim

2013

Korean J Thorac Cardiovasc Surg

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BackgroundIschemic 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.MethodsExtracted 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 (1.0×107 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.ResultsThe 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.ConclusionThe 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.

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Section: Discussionmentioning

confidence: 99%

Influence of Mesenchymal Stem Cells on Cryopreserved Tracheal Allografts in Rabbits

Kim

2013

Korean J Thorac Cardiovasc Surg

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“…The murine model of orthotopic tracheal transplantation that was adopted in this study has proved to be a good model for experimental study of the reepithelialization of the tracheal graft. [3][4][5][6] With murine orthotopic and heterotopic tracheal transplantation models, it has been proved that immunosuppressors can be withdrawn without inciting acute and chronic rejection if the donor epithelium is progressively replaced by recipient-derived epithelium. 4,5 It takes at least a 48-day period to complete reepithelialization in immunosuppressed orthotopic tracheal allografts, 6 however, so it is necessary to find a way to accelerate the epithelial regeneration of the tracheal graft.…”

Section: Discussionmentioning

confidence: 99%

“…Because the epithelium of donor has been thought to be the primary target of allograft rejection, 2 reepithelialization of orthotopic tracheal grafts with recipientderived epithelium may be a great help in preventing airway obliteration and rejection. [3][4][5] Tracheal reepithelialization takes a long time, 6 however, so finding a way to accelerate the epithelium regeneration may contribute to the success of tracheal transplant.…”

mentioning

confidence: 99%

Sustained local application of epidermal growth factor to accelerate reepithelialization of tracheal grafts

Zhao

Han

Liang

et al. 2010

The Journal of Thoracic and Cardiovascular Surgery

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“…[10][11][12][13] Given the immunoprivileged nature of chondrocytes, complete decellularization of donor trachea may not be necessary for a suitable tracheal replacement. [14][15][16][17] Contemporary approaches have begun to assess the feasibility of partial decellularization approaches, removing immunogenic cell types and preserving immunoprivileged chondrocytes. 18,19 We have developed a mouse model of orthotopic tracheal replacement which permits the assessment of the tracheal replacements in vivo.…”

Section: Introductionmentioning

confidence: 99%

Regeneration of partially decellularized tracheal scaffolds in a mouse model of orthotopic tracheal replacement

et al. 2021

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Decellularized tracheal scaffolds offer a potential solution for the repair of long-segment tracheal defects. However, complete decellularization of trachea is complicated by tracheal collapse. We created a partially decellularized tracheal scaffold (DTS) and characterized regeneration in a mouse model of tracheal transplantation. All cell populations except chondrocytes were eliminated from DTS. DTS maintained graft integrity as well as its predominant extracellular matrix (ECM) proteins. We then assessed the performance of DTS in vivo. Grafts formed a functional epithelium by study endpoint (28 days). While initial chondrocyte viability was low, this was found to improve in vivo. We then used atomic force microscopy to quantify micromechanical properties of DTS, demonstrating that orthotopic implantation and graft regeneration lead to the restoration of native tracheal rigidity. We conclude that DTS preserves the cartilage ECM, supports neo-epithelialization, endothelialization and chondrocyte viability, and can serve as a potential solution for long-segment tracheal defects.

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Reepithelialized Orthotopic Tracheal Allografts Expand Memory Cytotoxic T Lymphocytes But Show No Evidence of Chronic Rejection

Cited by 11 publications

References 28 publications

Influence of Mesenchymal Stem Cells on Cryopreserved Tracheal Allografts in Rabbits

Influence of Mesenchymal Stem Cells on Cryopreserved Tracheal Allografts in Rabbits

Sustained local application of epidermal growth factor to accelerate reepithelialization of tracheal grafts

Regeneration of partially decellularized tracheal scaffolds in a mouse model of orthotopic tracheal replacement

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