Pig tracheal patchy xenotransplantation in the dog

Abstract

A long-segmental tracheal lesion is difficult to repair by tracheal allotransplantation due to the lack of a well-defined blood supply for blood vessel anastomosis. The donor trachea needs to be revascularized within a well-vascularized soft tissue flap for several months to allow successful trachea allotransplantation. To date, xenotransplantation using the wild-type or genetically modified pig has been widely studied. The object of this study was to evaluate the feasibility of a small-sized (2×2cm) wild-type pig tracheal patchy in a dog tracheal defect model before trying a long-segment tracheal defect model and using a genetically modified pig as a donor in dog xenotransplantation. Three healthy beagle dogs (8-9kg) were used as recipients, and one pig (20kg) was used as the donor. A pig cartilaginous tracheal patchy (2×2cm half tube) was sutured to the tracheal resected site in each dog. Antithymocyte globulin (2.5mg/kg infusion, D0 and 1), tacrolimus (4.5mg/kg, twice a day for 2months), and methylprednisolone sodium succinate (1mg/kg, IV, for 2days and tapering) were administered for immunosuppression. The levels IL-2 and IFN-γ in the serum were measured at D0, 7, and 28. Tracheoscopy was performed at D28, 60, and 90. The recipients were sacrificed at D90, and the expression of dog and pig genes in the graft was evaluated by PCR. Histopathological examination of the graft was conducted. All of the dogs survived without complications during the experimental period. Their IL-2 and IFN-γ levels were significantly increased at D7 after transplantation compared to D0 and D28 (P<0.05). The pig tracheal patchy site was open, and no stenosis was observed until D90 on tracheoscopy, when pale mucosa erosion was observed; there was also remnant suture material at D28. However, the tracheal patchy sites gradually became similar to normal mucosa at D60 and 90. The expression of pig genes was detected in the graft by PCR. Normal epithelium and CD3 cells were observed in the histological examination at D90. In this study, our data suggest that the pig tracheal patchy can be successfully engrafted into the trachea of dog, although erosion of mucosa on the graft was seen at D30, in spite of the discordant species.