Plastic Surgery Research Council
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PSRC 60th Annual Meeting

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Tracheal Allotransplantation: The Next Step.
Margot Den Hondt, MD, Pierre Delaere, MD, PhD, Jan Jeroen Vranckx, MD, PhD.
KULeuven, Leuven, Belgium.

PURPOSE:
Key elements in tracheal allotransplantation are adequate vascularization, a stable framework withstanding respiratory forces and an inner mucosal lining, thus preventing healing by secondary intention and subsequent stenosis. Since we are dealing with allogenic tissues, rejection of the respiratory epithelium remains of great concern.
METHODS: We transplant an allogenic tracheal segment into the lateral thoracic fascia of the New Zealand White rabbit. Rabbits receive full dose immunosuppression, i.e. tacrolimus. Tapering of tacrolimus induces a silent rejection of the inner mucosal lining. By replacing donor epithelium with recipient mucosa, we eliminate the allogenic component. After a 14-day heterotopic prefabrication period, we perform an orthotopic transfer of the segment to the neck. We cultured ciliated epithelium from tracheal inner lining to subconfluence. Cells in passage three were used as a patch of neo-epithelium on an inner lining defect in the rabbit model. Gradually the size of defects was enlarged and cell migration observed on histological sections. We decellularized a rabbit trachea tube using controlled enzymatic digestion protocols. Aim was to preserve structural integrity while removing cellular components. Subsequently these trachea’s were covered with the cultivated ciliated epithelium. Blood outgrowth endothelial cells (BOECs) were cultured from rabbit intravenous blood and added to the construct to enhance vascularization. In the human model, we observed an avascular necrosis of the posterior tracheal wall during heterotopic revascularization of the tracheal segment in the radial forearm fascia. Since little lumen is preserved by primary anastomosis of the cartilage rings, we perform an additional reconstruction of the membranous trachea with cartilage in the rabbit model.
RESULTS: As we demonstrated by creating a full thickness mucosal defect in the rabbit model, bare cartilage will lead to recurrent stenosis. After enzymatic decellularization, the rabbit trachea preserves its rigidity and the structural elements necessary for cellular adhesion. Ciliated epithelium could be efficiently cultivated and led to reepithelialization on decellularized tracheal tubes of various sizes. These ‘cell-engineered ‘ tubes could be efficiently prefabricated using our lateral thoracic pedicle. BOECs could be cultivated from intravenous rabbit blood and led in vitro to the formation of vascular structures. In vivo, adding BOECs accelerated healing of the reepithelialized tracheal tubes. By cartilaginous reconstruction of the posterior wall, we preserved adequate diameter of the tracheal lumen to allow for normal breathing.
CONCLUSION:Up until now, five patients in our center received a tracheal allotransplantation with withdrawal of immunosuppression. To reconstruct a long segment tracheal stenosis, it is of utmost importance to provide a vascularized inner mucosal lining. We modified the time points in our protocol to reduce the adverse effects of immunologic rejection. Currently we are fine-tuning the enzymatic treatment of the inner lining and cultivation of mucosa in the rabbit model.


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