Grafting Islets to a Prevascularized Subcutaneous Site to Improve Transplant Survival and Function: A Mouse Model

The subcutaneous space is regarded as a potential site for islet transplantation; however, hypoxic conditions are a major drawback. We hypothesized that islet transplantation into a prevascularized subcutaneous space created using in-body tissue architecture technology would improve islet engraftment and contribute to maintaining the function of transplanted islets.

Five hundred syngeneic islets were transplanted into the prevascularized subcutaneous space (PSS) constructed by the implantation of a silicone rod for 2 weeks in C57BL/6J diabetic mice. Diabetic mice transplanted with islets into the unmodified subcutaneous space (USS) were used as the controls. After transplantation, nonfasting blood glucose levels were monitored for 8 weeks, and an intraperitoneal glucose tolerance test and histological evaluation were performed.

Five of the 10 recipients in the PSS group and two of the nine recipients in the USS group returned to normoglycemia. Engraftment of the transplanted islets was detected in nine of the 10 recipients in the PSS group, and the engraftment rate in the PSS group was significantly higher than that in the USS group (P = .005). Intraperitoneal glucose tolerance test results showed that the glucose tolerance of recipient mice in the PSS group was significantly better than that of the diabetic mice. Histological analysis revealed that the density of capillary vessels in the connective tissue surrounding the engrafted islets in the PSS group was significantly higher than that in the USS group (41.7/mm² vs 7.2/mm², P < .01).

Islet transplantation into the PSS using in-body tissue architecture technology has the potential to improve graft survival.