The Role of Cd4+ Helper T Cells in the Destruction of Microencapsulated Islet Xenografts in Nod Mice

Weber, Collin J.; Zabinski, S; T, Koschitzky; Wicker, Linda S.; Rajotte, Ray V.; D’Agati, Vivette D.; Peterson, Laurence B.; Norton, Janet; Reemtsma, K

doi:10.1097/00007890-199002000-00034

Cited by 122 publications

(70 citation statements)

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“…Repeated attempts by several investigators since then have failed to demonstrate reversal of diabetes by this method in large animal models (1)(2)(3)(4)(5), thus frustrating the clinical application of encapsulated islets.…”

mentioning

confidence: 99%

Long-term reversal of diabetes by the injection of immunoprotected islets.

Soon‐Shiong

Feldman

Nelson

et al. 1993

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

228

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mentioning

confidence: 99%

Long-term reversal of diabetes by the injection of immunoprotected islets.

Soon‐Shiong

Feldman

Nelson

et al. 1993

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

228

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“…Unlike human, dogs possess the Gal-α 1-3 Gal epitope. It has been reported that the destruction of discordant islet xenografts was mediated by immunological cells [41]. The necrosis observed here may have been due to hypoxia occurring after the encapsulation of the fibrous tissue around the Bio-AEP, rather than to an immunological rejection.…”

Section: Discussionmentioning

confidence: 58%

Xenotransplantation of Porcine Pancreatic Endocrine Cells to Total Pancreatectomized Dogs

Edamura

Itakura

Nasu

et al. 2003

The Journal of Veterinary Medical Science

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ABSTRACT. Xenotransplantation of porcine pancreatic endocrine (PE) cells in a diffusion chamber, a bioartificial endocrine pancreas (Bio-AEP), was conducted to total pancreatectomized dogs. Six pancreatectomized dogs were divided into two groups of 3 dogs each. In three dogs of the control group, exogenous insulin was administered twice a day for 30 weeks to maintain fasting blood glucose (FBG) levels within the normal range. The remaining three dogs were implanted with Bio-AEPs (implantation group), in addition to daily insulin administration. In the implantation group, Bio-AEPs containing 1.3 to 1.8 × 10 7 cells per kg of body weight of the recipient were implanted without fixation into the abdominal cavity. In the control group, exogenous insulin requirements did not decrease during the experimental period, whereas it significantly decreased for a certain period (3, 11, 17 weeks) after implantation in all implanted dogs. In the implantation group, laparotomy was performed after FBG and the exogenous insulin requirement increased again and Bio-AEPs were removed. Two Bio-AEPs were completely destroyed, and the remaining one was encapsulated by thin fibrous tissue. In this dog, effusion was present within the capsule, but the Bio-AEP was not destroyed. Histopathologically, the necrosis, presumably caused by hypoxia, of the PE-cells was observed on transmission electron microscopy. In conclusion, Bio-AEP could function for a certain period after implantation in this study. However, more preclinical researches should be needed to apply this technique for the treatme nt of diabetic dogs.

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“…Weber et al (8) found that alginate/poly(lysine) microcapsules containing 4 x 103 to 1.2 x 104 canine isletstt functioned for only 11.5 + 3 days (range, 5-17 days) in nonobese diabetic mice. With anti-CD4 monoclonal antibody treatment, however, long-term functional survival was observed for 4/8 (50%) recipients.…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…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.…”

mentioning

confidence: 99%

See 1 more Smart Citation

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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The Role of Cd4+ Helper T Cells in the Destruction of Microencapsulated Islet Xenografts in Nod Mice

Cited by 122 publications

References 0 publications

Long-term reversal of diabetes by the injection of immunoprotected islets.

Long-term reversal of diabetes by the injection of immunoprotected islets.

Xenotransplantation of Porcine Pancreatic Endocrine Cells to Total Pancreatectomized Dogs

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

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