Experimental research of discordant tracheal xenotransplantation

OBJECTIVE: To investigate the immunological rejection mechanism of tracheal xenotransplantation and xenografts as potential sources of trachea. METHODS: On SD rat model, a xenotransplanted tracheal from the guinea pig was established by wrapping it in the cervical muscles in situ. It was divided into cryopreserved group and uncryopreserved group. Under the examinations with histochemistry, immunofluorescence (IFL) and flow cytometry (FCM) techniques, the pathomorphological characteristics of the tracheal xenografts and the immunological rejection mechanism were evaluated. RESULTS: The tracheal allotransplantation with cryopreserved grafts wrapped by neck muscles was survived for a longer period. Histological examination revealed normal appearance of the allografts. The tracheal grafts patency was above 80%. However, cryopreserved tracheal xenografts of the guinea pig-to-rat maintained vitality for 14 days in maximum and 13.2 days on average, while the fresh tracheal xenografts only for 9 days in maximum, and 8 days on average. Acute rejection occurred in the tracheal xenotransplantation. A marked mononuclear-macrophage cellular infiltration mixed with eosinophils and lymphocyte was seen in the xenografts. Antibody (IgM, IgG) and complement (C3) deposition were also obviously detected by IFL in the xenografts. CD4 T+ cells and CD8+ T cells increased significantly in the vascular circulation. In all of the xenografts, complete loss of tracheal epithelium was associated with cartilage necrosis. The grafts patency was below 50%. This performance deteriorated with extended time periods. The fresh xenografts performed significantly worse than the cryopreserved xenografts. CONCLUSIONS: Acute rejection, caused by humoral immune reaction mainly integrated with cellular immunity, is the most notable characteristics in the guinea pig-to-rat tracheal xenotransplantation in situ. Cryopreservation can potentially reduce the antigenicity. The low antigenicity may inhibit the immunologic reaction relatively, so that prolonged survival of discordant cryopreserved tracheal xenografts could be achieved.