REGIMENS OF IGF-I TREATMENT IN FETAL PANCREAS TRANSPLANTATION

Transplantation of fetal pancreas (FP) is a potential treatment for di abetes mellitus, FP has remarkable proliferative capacity and may be i nduced to expand sufficiently to provide a functional beta cell mass i n adult recipients. We have demonstrated that local delivery of recomb inant insulin-like growth factor-I (IGF-I) onto FP isografts is suffic ient to reverse streptozotocin-induced diabetes in animals receiving a s few as 4 fetal pancreata. In this current study we investigated othe r regimens of IGF-I delivery in an attempt to define whether its effec ts on FP required local delivery or whether other, more clinically fea sible, forms of treatment would suffice. In our model, diabetic Lewis rats received isografts of 16 FP into the anterior thigh intramuscular (WI) site. In the group of FP recipients treated with vehicle alone, no animals converted to euglycemia (0/8). When the IM site was pretrea ted locally with 14 days of continuous IGF-I administration (69 mu g/k g per day) prior to FP transplantation, 100% of the recipients (10/10) became euglycemic with a mean interval from transplant to euglycemia of 35 +/- 15 days (P < 0.001 when compared to vehicle alone). No signi ficant advantage over the vehicle alone group was gained either when t he FP tissue was cultured for 48 hr in the presence of IGF-I (100 mu g /ml) and then implanted (27% conversion to euglycemia, 3/11) or when F P isografts were treated with continuous subcutaneous delivery of IGF- I (69 mu g/kg per day over 14 days) distant from the transplant site ( 0% conversion to euglycemia, 0/6), IGF-I increased the rate of convers ion to euglycemia either when delivered locally to FP isografts or whe n delivered to the transplant bed prior to transplantation. This sugge sts an active role of the IGF-I-treated transplant bed in the success of FP transplantation. (C) 1997 Academic Press.