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PS3.3 Assessment of diabetic recipient model using Japanese monkey for islet xenotransplantation

Naoaki Sakata, Japan

Associate Professor
Department of Regenerative Medicine & Transplantation
Fukuoka University

Abstract

Assessment of diabetic recipient model using Japanese monkey for islet xenotransplantation

Naoaki Sakata1,2, Ryo Kawakami1,2, Teppei Yamada1,2, Gumpei Yoshimatsu1,2, Shohta Kodama1,2.

1Department of Regenerative Medicine and Transplantation, Fukuoka University, Fukuoka, Japan; 2Center for Regenerative Medicine, Fukuoka University Hospital, Fukuoka, Japan

While pancreatic islet transplantation is known as an effective therapy for severe diabetic patients, the number of the cases has not been increased. One major limitation of this therapy is in donor supply in Japan. Porcine islet xenotransplantation is considered as an ideal alternative therapy which resolves the problems in limited donor supplies. To achieve this treatment in a clinical setting, preclinical studies using nun-human primates (NHPs) are essential. Recently, we have attempted to perform preclinical porcine islet xenotransplantation using Japanese monkey (Macaca fuscata), a NHP belongs to macaque endemic to Japan. While Japanese monkeys have been used for various animal studies including infection, there are no previous studies about porcine islet xenotransplantation using this animal. In other words, Japanese monkeys are not fully established as a recipient animal model for islet transplantation yet. Especially, there are no information about induction of diabetes using this animal. In this study, we tried to show the preferable methods of induction of diabetes using Japanese monkey for islet transplantation. Twenty-nine Japanese monkeys received treatments for induction of diabetes including pancreatectomy (n = 5; total pancreatectomy n = 3, subtotal pancreatectomy n = 2; group 1), pancreatectomy with administration of low dose streptozotocin (STZ, 45 - 70 mg/kg) (n = 4; group 2), administration of one-shot STZ (n = 8; 50 mg/kg n = 3, 80 mg/kg n = 1, 100 mg/kg n = 3, 110 mg/kg n = 1; group 3) and administration of continuous administrations of low dose STZ (n = 2; group 4). They were assessed in blood glucose, achievement of diabetes (defined as >200 mg/dL in blood glucose), complications and survival. The characteristics among the groups were almost similar (median age (years): 10 in group 1, 8.5 in group 2, 8 in group 3, 10 in group 4; mean body weight (kg): 13.18 ± 0.51 in group 1, 11.35 ± 1.08 in group 2, 11.46 ± 0.78 in group 3, 8.55 ± 0.25 in group 4; blood glucose before diabetes induction (mg/dL): 64.23 ± 4.02 in group 1, 61.75 ± 4.26 in group 2, 79.67 ± 8.70 in group 3, 62.78 ± 1.61 in group 4). Diabetic condition might be milder in group 4 comparing with other groups (blood glucose after diabetes induction (mg/dL): 225.32 ± 41.58 in group 1, 187.72 ± 56.27 in group 2, 170.78 ± 41.62 in group 3, 110.92 ± 13.03 in group 4), however, achievement of diabetes rate and survival were the highest in this group (diabetes rate (%): 100 (5/5) in group 1, 50 (2/4) in group 2, 50 (4/8) in group 3, 100 (2/2) in group 4; survival rate (%): 20 (1/5) in group 1, 100 (4/4) in group 2, 37.5 (3/8) in group 3, 100 (2/2) in group 4). Assessment of group 3 indicates that the dose of STZ for induction of diabetes was variable and preferable dose was hardly established. Our data reveal that administration of continuous administrations of low dose STZ is preferable method for Japanese monkey to induce diabetes in reliability and safety.

References:

[1] Xenotransplantation
[2] Islet transplantation
[3] Diabetes
[4] Recipient
[5] Monkey

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