OUTCOME OF SUBCUTANEOUS ISLET TRANSPLANTATION IMPROVED BY POLYMER DEVICE

Syngeneic transplantation of rat islets into subcutaneous tissue faile d to cure streptozocin diabetes, The reason is unknown, but poor vascu larization 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 compare d 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 tis sue site achieved normoglycemia, To create vascularized organoids, we transplanted 800 mouse islets into polyvinyl alcohol (PVA) or polyglyc olic acid (PGA) polymers in subcutaneous tissue of streptozocin-diabet ic mice either immediately (four in PVA and six in PGA) or 7 days (fou r in PVA and four in PGA) after implantation, Four weeks after transpl antation, the mean blood glucose level and body weight had no change w ith PVA, However, the mean body weight increased significantly with PG A and 3/10 became normoglycemic. When transplanting 400 islets with PG A polymers intraperitoneally, all animals (n=5) remained hyperglycemic 3 months later. In contrast, four of five recipients transplanted wit h 800 islets with PGA polymers subcutaneously became normoglycemic, Th e grafts from successful animals contained numerous revascularized isl ets containing a substantial amount of insulin. These preliminary resu lts indicate that subcutaneous islet transplantation using PGA polymer s can improve the metabolic status and, in some cases, even cure diabe tes in streptozocin-diabetic mice.