Transplantation of normal isolated islets of langerhans for the treatment of diabetes remains an elusive goal in clinical practice. Perhaps the major problem preventing clinical islet transplantation has been limited by the inability to prevent islet allograft or xenograft rejection. Cyclosporin A is an immunosuppressive agent that improves survival of transplant. This exciting immunosuppressive agent was first used clinically in renal transplantation in 1978 (Ferguson and Fidlus 1982).The aim of this study was the isolation , purification and transplantation of hamster pancreatic islet as xenograft transplantation for the treatment of diabetic mice. It is also aimed to study the effect of cyclosporin A as an immunosuppressive agent on some biochemical parameters e.g blood glucose and blood insulin levels to induce maximum suppression of mice immune system and consequently realizing maximum survival of transplanted islets. A total of 30 streptozotocin induced mice were randomized to receive islets xenografts from golden syrian hamsters by three different approaches ,the first group of ten mice received islets only in the renal subcapsular space, the 2 nd of ten mice received islets in the renal subcapsular space and was given cyclosporin A in a dose of 15 mg/kg/day for three days.The 3 rd group of ten mice were received islets in the renal subcapsular space and were given cyclosporin A orally every day at a dose of 15 mg/kg/day for three days which was gradually decreased to 5 mg/kg/day. Non of the mice of group 1 became normoglycemic. All mice of group 2 became normoglycemic for 11±4 ( range 6-18 days) . only mice of group 3 enjoyed normoglycemic as long as cyclosporin-A was administrated. Consequantly, prolonged survival of islets xenografts may be achieved with administration of cyclosporin-A. Introduction:
Prevention of rejection is critical to achieve successful pancreatic islet transplantation protection of islet cells from rejection by isolating the islets in artificial membranes has been used instead of immunosuppression treatment. In these study we investigated the microencapsulation of microencapsulated hamster islets in hydrophilic microencapsules made of agarose. The microencapsulated hamster islets were placed interaperitoneally in mice in which diabetes was induced by a single dose (150 mg/kgof body weight) of streptozotocin. Five groups were studied. The first group (5 mice) received free hamster islets (1000 islets).The second group (5 mice) received 1000 empty agarose microcapsules and 1000 free hamster islets. The third group (10 mice) received hamster islets microencapsulated in agarose (500 microcapsules). The forth group (10 mice) received 1000islet microcapsules. The fifth group (10 mice) received 1000 islet microcapsules cultured in CMRL-1066 medium for 4 weeks at 37C. Mice of group 1 and group 2 failed to achieve normoglycemia. Recepient mice received miccroencapsulated islets group (3,4,5) maintained normoglycemia for a mean of 45 ± 5 days range (30-65 days). These cured mice had normal glucose tolerance tests, which indicates that islets in the microcapsules were functioning as if they are in an intact pancreas. Microcapsules, retrieved up to 30 days after transplantation, showed no evidence of tissue reaction. Our study indicate that agarose microcapsules can protect islet xenografts from rejection. These microcapsules may be suitable for human clinical islet xenotransplantation. Introduction: Pancreatic islets transplantation for the treatment of human diabetes has been limited by the inability to prevent islets rejection. Various approaches for preventing islet graft rejection and thus maintaining long term islet cell function has been investigated (Lacy, 1993). One of these approaches is the protection of the transplanted islet from recipient immune system by enclosing them in membranes that prevent inward diffusion by immune mediators, but allow free exchange of glucose and insulin (De-Vas et al., 2002 and Kabayashi et al., 2003) Previous studies had demonstrated that islet can be entrapped in viable state in alginate capsules which are characterized by a shell of alginate-polyethyleneimine
Cyclosporin A is an immunosuppressive agent that improves survival of transplant. This exciting immunosuppressive agent was first used clinically in renal transplantation (Ferguson and Fidlus 1982).The aim of this study was the isolation , purification and transplantation of hamster pancreatic islet as xenograft transplantation for the treatment of diabetic rats. It is also aimed to study the effect of cyclosporin A as an immunosuppressive agent on some biochemical parameters e.g blood glucose and blood insulin levels to induce maximum suppression of mice immune system and consequently realizing maximum survival of transplanted islets. A total of 30 streptozotocin induced rat were randomized to receive islets xenografts from golden syrian hamsters by three different approaches ,the first group of ten rats received islets only in the renal subcapsular space, the 2 nd of ten rats received islets in the renal subcapsular space and was given cyclosporin A in a dose of 30 mg/kg/day for three days only.The 3 rd group of ten rats were received islets in the renal subcapsular space and were given cyclosporin A orally every day at a dose of 30 mg/kg/day for three days which was gradually decreased to 10 mg/kg/day. Non of rats of group 1 became normoglycemic. All rats of group 2 became normoglycemic for 228± (range 12-36 days). Only rats of group 3 enjoyed normoglycemic as long as cyclosporin-A was administrated. Consequantly, prolonged survival of islets xenografts may be achieved with administration of cyclosporin-A (Springer,et al., 2015).
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