A large-animal model to evaluate the clinical potential of fetal pig pancreas fragment transplantation

The long-term goal of this study is to assess the feasibility of using feta l pig pancreas fragment (FPPF) transplantation to treat patients with type I diabetes. Using the highly inbred Westran Pigs, our initial aim was to es tablish a rejection-free transplant model of FPPF grafted into sibling reci pient pigs without immunosuppression. FPPFs were isolated from 80-100-day-o ld fetuses of either Westran Pigs or outbred pigs and transplanted into the thymus, spleen, liver, or kidney of the recipient Westran pig. Biopsies we re taken from each transplant site at set time points and assessed histolog ically for islet viability, rejection, and endocrine function. Fifty-eight fetal donors were used to transplant 16 recipient pigs. A nonspecific infla mmation was seen for both outbred and inbred FPPF donor tissue at day 3 and was considered a response to ischemic necrosis. However, all the transplan ted outbred FPPF donor tissue was acutely rejected and lost by day 10-14. I n contrast, inbred FPPF tissue showed little evidence of graft necrosis aft er 3 days, and growth and formation of epithelial islet cell nest-like stru ctures were seen to 28 days after transplantation. With time after transpla ntation, increasing amounts of insulin immunoperoxidase staining was seen t ogether with chromogranin and somatostatin staining. In summary, this study confirms the potential of the Westran pig to answer the unproven ability o f fetal pancreatic tissue to reverse type I diabetes in a large animal mode l.