The Japanese Macaque as a Diabetes Recipient Animal Model for Porcine Islet Xenotransplantation

Porcine islet xenotransplantation is effective for severe diabetes; however, preclinical studies are essential. In this study, we evaluated the suitability of the Japanese macaque as a recipient model for islet xenotransplantation, including identifying the preferred method to induce diabetes. The safety and stability of the following four models to induce diabetes were assessed: Model 1: pancreatectomy, Model 2: pancreatectomy with low-dose streptozotocin (STZ), Model 3: single-injection of STZ, and Model 4: consecutive administrations of low-dose STZ. Diabetes was induced in all four models. The blood glucose level after induction of diabetes was 225.32 ± 46.49 mg/dL in Model 1, 209.64 ± 64.36 mg/dL in Model 2, 175.51 ± 45.18 mg/dL in Model 3, and 139.22 ± 6.31 mg/dL in Model 4. Regarding safety, Models 1 and 2 involved invasive surgery with postoperative concerns. Model 3 induced diabetes in the Japanese macaques; however, the preferable dose of STZ was individual dependent. Among the models, Model 4 was preferable regarding safety and stability. Finally, we performed porcine islet xenotransplantation in a diabetic monkey in Model 4 and evaluated the therapeutic effects of this treatment. In conclusion, the Japanese macaque might be a possible recipient model for porcine islet xenotransplantation.