Background: The mouse is still considered the premier model in basic immunologic and transplant-related research. However, because of its much smaller size, the mouse has proven to be a technically difficult and physiologically fragile model from a surgical standpoint. That is why only a few studies currently use mouse models in vascularized composite allotransplantation. The purpose of this study therefore was to develop a reproducible and reliable surgical technique in the mouse for future vascularized composite allotransplantation studies.
Methods: Forty DBA/2 (H2-Dd) hindlimb osteomyocutanous flaps were transplanted into the right cervical region of C57BL/6 (H2-Db) mice using a nonsuture cuff technique. The donor iliac artery and femoral vein were mounted with polyimide cuffs (inner diameter, 0.404 mm; wall thickness, 0.025 mm) and subsequently anastomosed to the recipient common carotid artery and external jugular vein. Immunosuppressant drugs were used postoperatively.
Results: The overall success rate was 85.0 percent (34 of 40). The mortality rate was 12.5 percent (five of 40); all deaths resulted from perioperative bleeding. Only one arterial insufficiency was encountered after transplantation. The operative time was approximately 2 hours. Indefinite allograft survival (>120 days) could be achieved using a specific immunosuppressant regimen.
Conclusions: This novel mouse model allows performing vascularized composite allotransplantation with very high success and survival rates. The advantages over conventional models are multifold. A high-flow common carotid artery keeps the anastomosis patent, and diastolic suction of the heart reduces the risk of venous stasis and thrombus formation. Less destruction because of the heterotopic positioning of the hindlimb graft further reduces the associated mortality and morbidity in this fragile model.