Development of a Standardized Animal Model for Simultaneous Solid Organ Transplantation and Sentinel Vascularized Composite Allotransplantation

Background In 2001, the first combined kidney with skin transplantation was performed in humans. Due to high immunogenicity of the skin graft, it may serve as a sentinel flap for simultaneously transplanted organs, potentially enabling a more precise prediction of organ rejection. To create a reproducible investigative method a novel rat model for simultaneous vascularized composite allotransplantation (VCA) and solid organ transplantation (SOT) was developed. Methods Left kidneys from male Dark Agouti rats (DA, RT1, n = 22) were removed and orthotopically transplanted to Lewis rats (LEW, RT1, n = 22). In addition, a vascularized full thickness hemi abdominal wall flap was transplanted as a sentinel flap. No systemic immunosuppression was administered postoperatively. Surgical steps and times were analyzed, and tissue samples were examined for ischemia-reperfusion injury, apoptosis and early signs of rejection. Results Donor surgery took on average 122 minutes ( 30 minutes). Recipient operation required 298 minutes ( 24 minutes). Histological evaluation showed no signs of rejection in the abdominal wall transplant (AWTX) 120 min after transplantation and 60 min in kidney transplants. An increase in ischemic damage with apoptotic cells and formation of tubular casts was detected in renal transplants. Conclusion To generate quantitative data for the benefit of SOT with VCA, an animal model of combined kidney and vascularized abdominal wall transplantation was created. Immediate postoperative histoevaluation showed evidence of ischemia-reperfusion injury and elevation of apoptosis. Further work will compare different endpoints and evaluate whether rejection episodes could be detected by utilizing a VCA sentinel flap.