Fetal Pancreas Transplantation in Miniature Swine: II. Survival of Fetal Pig Pancreas Allografts Cultured at Room Temperature

Islet-allograft survival has been shown to be markedly prolonged in rodents when donor tissue has been precultured at 24°C. In this study, the feasibility of this approach was tested in NIH minipigs transplanted with fetal pancreases. Collagenase-digested fetal pig pancreatic tissues survived in culture at 24°C for 6–7 days and continued to grow in vitro at 37°C after being transferred. These tissues no longer stimulated allogeneic lymphocytes in vitro, although some tissues cultured at 37°C did. This allogeneic stimulation did not correlate to the number of major histocompatibility complex (MHC) class 11-positive cells in stimulator pancreatic cultures. When transplanted into an omentum pouch of normal, nonimmunosuppressed minipigs, fresh fetal pancreatic tissues were rejected within 14 days. Tissues cultured at 24°C grew, and β-cells proliferated in minipigs treated daily with cyclosporin A (CsA) and azathioprine. Twelve normal minipigs were transplanted with 24°C-cultured fetal pancreases: 8 pigs received no treatment, 2 received 14 mg · kg⁻¹ · day⁻¹ CsA for 14 days, and 2 received 6–7 intravenous injections of platelets prepared from pooled farm-pig blood before grafting. Strong lymphocytic infiltration was detected in all grafts removed between 30 and 90 days posttransplantation. However, β-cells were found on day 45 in one of five minipig pancreas grafts incompatible at the MHC loci and on days 60–90 in all three grafts compatible at MHC but incompatible at minor histocompatibility loci. Short-term CsA treatment did not prolong survival of allografts from farm pigs into minipigs. In contrast, some β-cells were detectable on day 30 in farm-pig pancreases grafted into 2 minipigs pretreated with platelets.