P-184

Total pancreatectomy and auto-islet transplantation in cynomolgus monkeys

B. Luo, S. Liu, H. Sun, F. Li
Xuanwu Hospital of Capital Medical University, General Surgery, Beijing, China

Objective: To examine the safety and efficacy of duodenum/spleen preserved total pancreatectomy to induce T1DM and to explore the effects of islets isolation and islets auto-transplantation in cynomolgus monkeys.

Methods: Ten male cynomolgus monkeys aged 4.5±1.1y and weighted 5.0±0.8 kg were used in this study. The total pancreatectomy was performed under the general anesthesia. Shortly, a midline incision was made, the pancreas was completely harvested as a whole organ in one monkey; otherwise, the body and tail of pancreas was removed without warm ischemia initially for islets isolation and then the head of pancreas was resected in another 9 monkeys. The pancreas was dissected from the spleen and arterial arcade around the duodenal was kept intact. For monkey islets isolation, 9 partial pancreas were perfused with Liberase HI at 1mg/ml via the pancreatic duct and isolated with Ricordi method without purification. 6 monkeys were simultaneously transplanted with auto-islets via portal vein after total pancreatectomy.

Results: 10 monkeys were pancreatecmized. One simultaneously islets auto-transplanted monkey died of bleeding on post-operative day 1. There was one common bile duct injure and a choledo-duodenal anastomosis was performed. No other surgical complications were found when the 9 monkeys survived from 10 days to 4 months. 3 monkeys without islet auto-transplant showed hyperglycemia even given twice insulin treatment daily. One month after pancreatectomy, insulin and C-peptide could not be detected by IVGTT in these 3 monkeys. 9 islets isolations were successful with an average yield at 13222±7730IEQ/g. Except one monkey died of bleeding, all other 5 auto-transplanted monkeys remained normoglycemia and free of insulin.

Conclusion: Total pancreatectomy is a safe procedure to induce T1DM. Successful monkey islets isolation could be repeated with LiberaseHI perfusion and Ricordi method. Unpurified auto islets transplant could reverse pancreatecmy-induced T1DM in monkeys.

P-184

Total pancreatectomy and auto-islet transplantation in cynomolgus monkeys

B. Luo, S. Liu, H. Sun, F. Li
Xuanwu Hospital of Capital Medical University, General Surgery, Beijing, China

Objective: To examine the safety and efficacy of duodenum/spleen preserved total pancreatectomy to induce T1DM and to explore the effects of islets isolation and islets auto-transplantation in cynomolgus monkeys.

Methods: Ten male cynomolgus monkeys aged 4.5±1.1y and weighted 5.0±0.8 kg were used in this study. The total pancreatectomy was performed under the general anesthesia. Shortly, a midline incision was made, the pancreas was completely harvested as a whole organ in one monkey; otherwise, the body and tail of pancreas was removed without warm ischemia initially for islets isolation and then the head of pancreas was resected in another 9 monkeys. The pancreas was dissected from the spleen and arterial arcade around the duodenal was kept intact. For monkey islets isolation, 9 partial pancreas were perfused with Liberase HI at 1mg/ml via the pancreatic duct and isolated with Ricordi method without purification. 6 monkeys were simultaneously transplanted with auto-islets via portal vein after total pancreatectomy.

Results: 10 monkeys were pancreatecmized. One simultaneously islets auto-transplanted monkey died of bleeding on post-operative day 1. There was one common bile duct injure and a choledo-duodenal anastomosis was performed. No other surgical complications were found when the 9 monkeys survived from 10 days to 4 months. 3 monkeys without islet auto-transplant showed hyperglycemia even given twice insulin treatment daily. One month after pancreatectomy, insulin and C-peptide could not be detected by IVGTT in these 3 monkeys. 9 islets isolations were successful with an average yield at 13222±7730IEQ/g. Except one monkey died of bleeding, all other 5 auto-transplanted monkeys remained normoglycemia and free of insulin.

Conclusion: Total pancreatectomy is a safe procedure to induce T1DM. Successful monkey islets isolation could be repeated with LiberaseHI perfusion and Ricordi method. Unpurified auto islets transplant could reverse pancreatecmy-induced T1DM in monkeys.