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G O'Shea

Publications and source records attributed to G O'Shea.

6 recordsLinked to original sources

Histological and immunopathological analysis of recovered encapsulated allogeneic islets from transplanted diabetic BB/W rats.

Allogeneic islets encapsulated in an alginate/poly-L-lysine membrane and transplanted into diabetic BB/W rats resulted in graft failure within 2 weeks of transplantation. Graft failure was associated with a dense pericapsular infiltrate (PCI) that resulted in necrosis of the encapsulated islets. The PCI could be inhibited by immunosuppressive agents, including cyclosporine and dexamethasone, and this resulted in a significant increase in graft survival. Immunopathological characterization of the PCI indicated that there was a predominance of macrophages. T helper cells also appeared to be present in this PCI. Empty capsules were also found to induce a similar PCI that was identical in composition to that found around encapsulated islets. Thus alginate/poly-L-lysine capsules do not appear to be biocompatible and may account for the variable results in islet graft survival found with these capsules.

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Transplantation of encapsulated allogeneic islets into diabetic BB/W rats. Effects of immunosuppression.

Allogeneic islets obtained from Lewis rats were transplanted into diabetic BB/W rats with or without cyclosporine. In addition, these islets were encapsulated in alginate-poly L-lysine membranes and then transplanted into diabetic BB/W rats with or without immunosuppressive and/or antiinflammatory agents. The agents used were cyclosporine, dexamethasone, indomethacin (Ind), or a combination of these. Our results show that islets alone survived for 7 days, with or without CsA therapy. Encapsulated islets survived for 14.2 days, and this was extended by CsA, Dex, or CsA + Ind. Loss of encapsulated graft functions was associated with formation of a dense pericapsular infiltrate, which was inhibited by CsA, Dex, CsA + Ind, or CsA + Dex. In addition, the infiltrate was reduced in animals that had diabetes for long periods of time (greater than 5 months versus less than 1 month). Empty capsules also provoked this cellular response. Thus, encapsulation of islets resulted in slightly prolonged islet survival, which was further enhanced by immunosuppression.

Animals↗

Microencapsulated cells as hormone delivery systems.

Transplantation of pancreatic islets of Langerhans has been shown to prevent the development of many of the complications associated with diabetes. Transplanted islets, however, are readily rejected by the immune system. The use of artificial membranes to isolate the transplanted islets from the immune system of the host prolongs islet allografts in experimental animals. We have developed a method for encapsulating islets in semipermeable membranes composed of alginate and polylysine. The same technique can be applied to other endocrine cell types. The capsules are 700 to 800 micron in diameter with a hydrogel membrane approximately 4 micron thick. Intraperitoneal allografts of 5 x 10(3) encapsulated islets reversed diabetes in rats for up to 21 months and intact capsules with viable beta cells could be recovered from the recipients. Microencapsulation of endocrine cells for transplantation could potentially be used in the clinical treatment of hormone deficiency diseases.

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