Microencapsulated islet grafts in the BB/E rat: a possible role for cytokines in graft failure

Cole, Della; Waterfall, Martin; McIntyre, Margaret; Baird, J. D.

doi:10.1007/bf00400922

Cited by 140 publications

(72 citation statements)

References 23 publications

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“…It is likely that, once recruited to the surroundings of the microcapsule, lymphokine-secreting cells injured the xenogeneic islets via soluble factors. This is in keeping with reports that the microcapsule membrane is permeable to the immunomodulatory polypeptide products of lymphocytes, macrophages/ monocytes, and natural killer cells of the immune system (2,25) and that anumber ofcytokines (interferon 'yand interleukin 2) and monokines (interleukin 1 and tumor necrosis factor) induce the degeneration of islet cells (26)(27)(28).…”

Section: Discussionsupporting

confidence: 89%

Xenotransplantation of canine, bovine, and porcine islets in diabetic rats without immunosuppression.

Lanza¹,

Butler²,

Borland³

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

141

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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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Section: Discussionsupporting

confidence: 89%

Xenotransplantation of canine, bovine, and porcine islets in diabetic rats without immunosuppression.

Lanza¹,

Butler²,

Borland³

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

141

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“…This could be relevant to islet transplantation, as XO may be activated by macrophages or hypoxia after graft implantation in the portal system. Thus, it is of particular interest to have a method that can reduce the deleterious effects of macrophage mediators that are implicated in islet graft primary non function [29±30] or in the destruction of microencapsulated islets [31].…”

Section: Discussionmentioning

confidence: 99%

Adenovirus-mediated catalase gene transfer reduces oxidant stress in human, porcine and rat pancreatic islets

et al. 1998

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“…Various factors have been implicated in the failure of encapsulated islets. A cellular reaction surrounding the capsules has often been observed, which could lead to depletion of oxygen and nutrients (14) or production of toxic cytokines (15). This accumulation of cells could be due to an immune response to the contained islets or to bioincompatibility of the capsular materials (16,17).…”

mentioning

confidence: 99%

Complete Protection of Islets Against Allorejection and Autoimmunity by a Simple Barium-Alginate Membrane

Duvivier‐Kali

Omer²,

Parent³

et al. 2001

Diabetes

263

199

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We describe a new technique for microencapsulation with high-mannuronic acid (high-M) alginate crosslinked with BaCl 2 without a traditional permselective component, which allows the production of biocompatible capsules that allow prolonged survival of syngeneic and allogeneic transplanted islets in diabetic BALB/c and NOD mice for >350 days. The normalization of the glycemia in the transplanted mice was associated with normal glucose profiles in response to intravenous glucose tolerance tests. After explantation of the capsules, all mice became hyperglycemic, demonstrating the efficacy of the encapsulated islets. The retrieved capsules were free of cellular overgrowth and islets responded to glucose stimulation with a 5-to 10-fold increase of insulin secretion. Transfer of splenocytes isolated from transplanted NOD mice to NOD/SCID mice adoptively transferred diabetes, indicating that NOD recipients maintained islet-specific autoimmunity. In conclusion, we have developed a simple technique for microencapsulation that prolongs islet survival without immunosuppression, providing complete protection against allorejection and the recurrence of autoimmune diabetes. Diabetes 50: 1698 -1705, 2001 I slet transplantation represents an important alternative for the treatment of type 1 diabetes but still requires immunosuppressive agents with their serious side effects (1). One approach to avoid such treatment is to protect islets from the host's immune system with a semipermeable, biocompatible membrane (2,3). Transplantation of islets contained in alginate-poly-L-lysine (PLL) capsules was first described by Lim and Sun (4). Numerous studies have shown successful reversal of diabetes by transplantation of islets enclosed in alginate-PLL capsules in streptozotocin-induced animals (5-9). However, limited success has been reported in spontaneously diabetic NOD mice, a model of autoimmune diabetes (10 -13). Various factors have been implicated in the failure of encapsulated islets. A cellular reaction surrounding the capsules has often been observed, which could lead to depletion of oxygen and nutrients (14) or production of toxic cytokines (15). This accumulation of cells could be due to an immune response to the contained islets or to bioincompatibility of the capsular materials (16,17). Failure might also be attributed to problems with ␤-cell viability in the capsules (18).Protection of porcine islets remains a goal of encapsulation, but xenografts might be more difficult to protect than allografts, as suggested by studies performed with permeable polymer membranes (19,20). This concept is important because of the improved prospects for obtaining an abundant supply of human ␤-cells from precursor cells (21,22). The goal of this study was to determine whether stable biocompatible alginate microcapsules without a permselective component, such as PLL or polyethylene-glycol, would be able to protect mouse islets against allorejection and autoimmunity. RESEARCH DESIGN AND METHODSIslet isolation. Islets were isolated from ma...

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Microencapsulated islet grafts in the BB/E rat: a possible role for cytokines in graft failure

Cited by 140 publications

References 23 publications

Xenotransplantation of canine, bovine, and porcine islets in diabetic rats without immunosuppression.

Xenotransplantation of canine, bovine, and porcine islets in diabetic rats without immunosuppression.

Adenovirus-mediated catalase gene transfer reduces oxidant stress in human, porcine and rat pancreatic islets

Complete Protection of Islets Against Allorejection and Autoimmunity by a Simple Barium-Alginate Membrane

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