Outcome of subcutaneous islet transplantation improved by polymer device

Syngeneic transplantation of rat islets into subcutaneous tissue failed to cure streptozocin diabetes. The reason is unknown, but poor vascularization may play a role. We hypothesize that if a well-vascularized subcutaneous site could be created, islet grafts would do well. Four hundred freshly isolated mouse islets were transplanted syngeneically under the renal capsule or into the intraperitoneal cavity and compared with 800 islets in subcutaneous tissue of streptozocin-diabetic mice. Four weeks after transplantation, 14 of 14 under the renal capsule, 4 of 8 in the intraperitoneal site, and 0 of 7 in the subcutaneous tissue site achieved normoglycemia. To create vascularized organoids, we transplanted 800 mouse islets into polyvinyl alcohol (PVA) or polyglycolic acid (PGA) polymers in subcutaneous tissue of streptozocin-diabetic mice either immediately (four in PVA and six in PGA) or 7 days (four in PVA and four in PGA) after implantation. Four weeks after transplantation, the mean blood glucose level and body weight had no change with PVA. However, the mean body weight increased significantly with PGA and 3/10 became normoglycemic. When transplanting 400 islets with PGA polymers intraperitoneally, all animals (n=5) remained hyperglycemic 3 months later. In contrast, four of five recipients transplanted with 800 islets with PGA polymers subcutaneously became normoglycemic. The grafts from successful animals contained numerous revascularized islets containing a substantial amount of insulin. These preliminary results indicate that subcutaneous islet transplantation using PGA polymers can improve the metabolic status and, in some cases, even cure diabetes in streptozocin-diabetic mice.