Comparative Study of Two Different Islet Transplantation Sites in Mice: Hepatic Sinus Tract vs Splenic Parenchyma

Abstract

Although 90% of clinical islet transplantations are performed via the portal vein approach, it is still far from the ideal transplant site. Alternative islet transplant sites are promising to reduce the islet dose required to reverse hyperglycemia, thereby improving the efficiency of islet transplantation. The aim of this study was to compare the differences in survival and metabolic function of islet grafts transplanted into the hepatic sinus tract (HST) and the splenic parenchyma (SP). Approximately 300 syngeneic mouse islets were transplanted into the HST (n = 6) and the SP (n = 6) of recipient diabetic mice, respectively. After transplantation, the glycemic control, glucose tolerance, and morphology of islet grafts were evaluated and compared in each group. The nonfasting blood glucose of the two groups of mice receiving islet transplantation gradually decreased to the normal range and sustained for more than 100 d. There is no significant difference in the time required to restore normoglycemia (P > 0.05). The results of the glucose tolerance test showed that the SP group presented a smaller area under the curve than the HST group (P < 0.05). Histopathological results showed that islet grafts in the HST and the SP were characterized with normal islet morphology and robust insulin production. Compared with the HST, islet transplantation in the SP presents better blood glucose regulation, although there is no significant difference in the time required to restore normoglycemia.