Permselective acrylic membranes were employed to prevent une rejection of discordant islet xenografts isolated from various large animals. Canine, porcine, and bovine islets were seeded into tubular diffusio abers and transplanted into the peritoneum of 27 nmmunosup pressed streptozotocin-induced diabetic Lewis rats. Si recipients received islet grafts from bovine calves, 7 receIved grafts from pigs, and 14 received grafts from dogs. Four of the latter were removed at 1 month. In the control group of 10 diabetic rats, 4 received nonencapsulted canine islets, 3 received nonencapsulated bovine islets, and 3 received nonencapated porcine islets. Recipients of encapsulated Islets promptly dropped from a pretranpaotation plasma glucose level of 487 ± 36 (mean ± SEM) to 84 ± 2 (canine), 81 ± 4 (bovine), and 81 ± 3 mg/dl (porcine) during the first week. 411 of the animals sustained theqe levels for at least 1 month. One rat taneously reverted to diabetes at 54 days taton; 4 other rats became hyperglycemic (glucose, >600 mg/di) after membrane removal on day 30. The rem 22 rats maintained fasting euglycema for >10 weeks. In contrast, rats that received Encapsulated Islets became hyperglycemic in <7 days. Intravenous glucose tolerance test K values (decline in glucose levels, %/min) at 1 month for the canine and bovine encapsulatedislet tr ant group were 3.5 ± 0.3 and 3.3 ± 0.1 compared with 3.3 ± 0.1 (P = 0.63) and 0.91 ± 0.1 (P < 0.0001) for normal (n = 4) and diabetic (n = 4) control groups. Morphologic studies of long-term functioning grafts (30-130 days) revealed well-preserved a, (3, and 8 (6) and pig (7) could enable the use of readily available supplies of large-animal donor tissue for islet grafting into human diabetics. Unfortunately, there is currently no clinically applicable immunologic method available that prevents the destruction of discordant islet xenografts (8)(9)(10)(11).Encouraged by the results obtained with the encapsulation of allogeneic and xenogeneic rodent islets in capillary hollow fibers (4, 12-14), we sought to determine whether larger tubular membrane diffusion chambers (fabricated from XM-50 acrylic copolymer) can protect xenografts of canine, bovine, and porcine islets from rejection in the absence ofany immunosuppressive drugs. Because the formation of fibrous tissue around the membrane has been a cause offailure in the past, a smooth external skin was used to minimize this host reaction.MATERIALS AND METHODS Animals. Adult male Lewis rats (Charles River Breeding Laboratories) weighing 250-300 g were used'as transplant recipients. Animals were fed ad libitum with a standard pelleted diet (Agway, no. 3000 RHM-Prolab) and allowed free access to water. Diabetes was induced by a single injection of streptozotocin (42 mg/kg of body weight in 0.01 M citrate buffer, pH 4.5; Sigma) into the tail vein 10-14 days prior to surgery. Only rats with plasma glucose levels >400 mg/dl were used in these studies. Fasting plasma glucose concentrations were measured by tail bleedings using -the gl...

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