409 How about Heparin-Pegylated islets in Allo-Islet Transplantation in Cynomolgus Monkeys
Tuesday November 17, 2015 from 07:00 to 08:00
Room 110

Hyojun Park, Korea


Transplantation division in department of surgery

Samsung Medical Center


How about Heparin-Pegylated islets in Allo-Islet Transplantation in Cynomolgus Monkeys

Hyojun Park1, Jae Berm Park 1, Sung Joo Kim1, Kyo won Lee1, Du Yeon Shin3, Yeongbeen Kwon 3, Sanghoon Lee1, Kaabsoo Kim2, Suk Koo Lee1.

1Department of Surgery, Samsung Medical Center,Sungkyunkwan University School of Medicine, Seoul , Korea; 2Department of anesthesiology , Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul , Korea; 3Transplantation Research Center, Samsung Biomedical Research Institute, Samsung Medical Center, Seoul , Korea

Much effort is devoted to the protection of islets during transplantation for clinical allo-islet transplantation to be successful with smaller number of transplanted islets. Pegylation is an effective way to protect islets by wrapping islets with various materials including heparin rapidly, with minimal loss of islets. Our goal was to achieve sufficient diabetes control by transplanting smaller numbers of heparin pegylated allo-islets. Male cynomolgus monkeys weighing 3.0 to 4.5 kg received simultaneous subtotal pancreatectomy and 60-80 mg/kg streptozotocin (STZ) injections to induce insulin-dependent diabetes. The pancreata procured from these animals were transplanted to monkeys that were previously made diabetic by the same method.

Islets 10,000 to 13,000 EIN/kg were transplanted into 10 cynomolgus monkeys (3 control group, 5 pegylation group and 10 heparin pegylation group). Induction immunosuppression was done with antithymocyte globulin 5mg/kg 4 times or ATG with rituximab (375mg/m2) and and tacrolimus/MMF was given as maintenance immunosuppression. Basal c-peptide at 2 months post-transplant was 1.76 ± 1.1 ng/ml in the heparin pegylation group, while it was 0.9 ± 0.8 ng/ml in the control group and 0.1 ± 0.1 ng/ml in the pegylation group. Monkeys transplanted with allo-islets undergone heparin pegylation were able to achieve partial insulin independence at 2 months post-transplant with mean 12,000 EIN/kg islets. Two monkeys that received heparin pegylated islets with ATG + rituximab induction are under stable blood glucose control with minimal use of insulin. This protocol requires more long-term follow-up.

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