Aim of study: Islet transplantation (IT) is a promising therapy strategy to treat type 1 diabetes. Non-human primate (NHP) is mainly used in pre-clinical phase for islet transplantation and surgical technique application into human. However, little was known about transplanted islet’s distribution in the whole liver and its characteristics. In this study, we confirmed the characteristics and locating tendency of the grafted islets in the liver of allo-islet transplanted cynomolgus monkey.
Methods: Four whole monkeys liver (about 1 to 5 month after IT) were divided into eight segment (S1~S8) by functional anatomy and fixed. Each segment was sectioned and then paraffin embedded. Using immunohistochemistry method, islet grafted liver slides were stained by H&E and insulin. Slide images were analyzed by Aperio positive pixel count V9 algorithm.
Results: Analyzed liver area of recipient monkeys were 9,369±511mm² to 16,569±794mm². The total number of counted islets in liver tissues was 102±13 to 631±51. Islet distribution in each segment of the all recipient’s liver were S1 (18.2±5.6%), S2 (22.7±11%), S3 (11.8±6.8%), S4 (18.8±4.8%), S5 (5.3±3.8%), S6 (5.4±4.8%), S7(5.9±4.2%) and S8(11.9±3.3%) respectively. When normalized to islet number per tissue area (100mm²), each segment present S1 (28.5±5.7%), S2 (13.9±6.6%), S3 (14.1±7.7%), S4 (12±1.7%), S5 (6.9±4.5%), S6 (4.8±4.2%), S7 (5.2±3.9%), S8 (14.7±4.6%) respectively and many islets were existed especially in the segment 1 in all recipient monkey. Grafted islet size (diameter) were 50.0um to 420.8um and the insulin positive area of islet was 0.37% to 92.49% in total 3,746 islets from four recipient monkeys.
Conclusion: We visualized islets in the whole liver of four recipient monkeys at a glance through IHC and islet characteristics. Our results indicate that the largest numbers of islets were existed in S1 than other segments (by islets per tissue area). Also, insulin positive area was higher in the smaller (50~100 um) than bigger size (100 um<) islets. Thus, S1 is more reasonable site for liver biopsy. So our analysis of characteristics in long term insulin independently survived monkey livers will provide information to clinical study.