Canine pancreatic fragment allotransplantation with cyclosporine A

Allograft rejection is the major obstacle to clinical pancreatic islet transplantation. We attempted Cyclosporine A (CsA) immunosuppression of intrasplenic pancreatic dispersed fragment allografts in unrelated, unmatched dogs. Animals underwent (1) pancreatectomy only, (2) autotransplantation, or allotransplantation with (3) no immunosuppression (NIL), (4) azathioprine (AZA 3 mg/kg/day) and prednisone (PRED 2 mg/kg/day), or (5) CsA (25 mg/kg/day). Graft preparation was by collagenase ductal perfusion and mechanical disruption and transplantation was by splenic venous reflux. Rejection was defined by permanent hyperglycemia (greater than 150 mg/dl). Apancreatic dogs survived 6.0 +/- 0.5 days; autotransplanted dogs remained normoglycemic at 6 months. Rejection occurred at NIL, 5.0 +/- 0.6 days; AZA/PRED, 1.8 +/- 0.3 days; and CsA, 19.3 +/- 5.6 days. Survival was NIL, 16.0 +/- 3.4 days; AZA/PRED, 13.4 +/- 1.4 days; and CsA, 33.3 +/- 4.6 days. CsA showed significant advantage over both groups in both time to rejection (P less than 0.05) and survival (P less than 0.01). CsA toxicity was minimal. CsA achieved significant delay in rejection and improved survival in unmatched, unrelated dogs after intrasplenic allotransplantation with pancreatic dispersed fragments.