Reversal of Diabetes in Pancreatectomized Pigs After Transplantation of Neonatal Porcine Islets

Reversal of Diabetes in Pancreatectomized Pigs After Transplantation of Neonatal Porcine Islets Tatsuya Kin 1 2 , Gregory S. Korbutt 1 2 , Tsunehiro Kobayashi 1 2 , Jannette M. Dufour 1 2 and Ray V. Rajotte 1 2 3 1 Department of Surgery, University of Alberta, Edmonton, Alberta, Canada 2 Surgical-Medical Research Institute, University of Alberta, Edmonton, Alberta, Canada 3 Department of Medicine, University of Alberta, Edmonton, Alberta, Canada Address correspondence and reprint requests to Ray V. Rajotte, Director, Surgical-Medical Research Institute, 1074 Dentistry/Pharmacy Centre, University of Alberta, Edmonton, AB, Canada T6G 2N8. E-mail: rrajotte{at}ualberta.ca Abstract Neonatal porcine islets (NPIs) are able to grow and to reverse hyperglycemia after transplantation in immunoincompetent mice. The aim of this study was to demonstrate the feasibility of allogeneic NPI grafts to achieve normoglycemia in a pancreatectomized diabetic pig. NPIs were isolated from pancreases of 1- to 3-day-old pigs, cultured, and then transplanted via the portal vein into the liver of totally pancreatectomized pigs (mean body weight, 20.8 kg). Each pig received NPIs consisting of 3.1 ± 0.3 × 10 6 β-cells/kg (12,476 ± 1,146 islet equivalent/kg). The six pigs that were given cyclosporine and sirolimus achieved normoglycemia by day 14 without insulin therapy. Three pigs died of surgical complications shortly after transplantation, whereas the other three remained insulin independent up to day 69. Of seven nonimmunosuppressed recipients, four pigs became normoglycemic by day 14 without insulin treatment, with two of the animals remaining normoglycemic long term. Well-preserved insulin-positive cells were found in the graft at the end of follow-up with a significant increase in insulin content in long-term survivors of both groups. This study demonstrates for the first time that allogeneic NPIs can reverse hyperglycemia in totally pancreatectomized diabetic pigs. CsA, cyclosporine HBSS, Hanks’ balanced salt solution IE, islet equivalent IVGTT, intravenous glucose tolerance test NPI, neonatal porcine islet RIA, radioimmunoassay Footnotes Accepted December 27, 2004. Received September 29, 2004. DIABETES