Immunosuppression, Macroencapsulation and Ultraviolet‐B Irradiation as Immunoprotection in Porcine Pancreatic Islet Xenotransplantation

Abstract: Membrane encapsulation or ultraviolet‐B irradiation, with or without mild immunosuppressive treatment, was applied in order to prolong the survival of xenogeneic porcine foetal pancreatic grafts. Non‐diabetic C57BL/6 mice were transplanted with porcine islet‐like cell clusters, either membrane‐encapsulated in the epididymal fat pad, or non‐encapsulated under the kidney capsule. The animals were treated with daily subcutaneous injections of either cyclosporin A (12.5 mg/kg b.wt.), 15‐deoxyspergualin (5.0 mg/kg b.wt.), ethyl (E)‐6‐(1, 3‐dihydro‐4‐hydroxy‐6‐methoxy‐7‐methyl‐3‐oxo‐5‐isobenzofuranyl)‐4‐methyl‐4‐hexenoate. (RS‐61443) (70 mg/kg b.wt.) or with cyclophosphamide (70 mg/kg b.wt.) every second day. A fulminant mononuclear cell infiltration was observed 14 days after transplantation both around the subcapsular graft and outside the membranes in the saline treated control group. The membrane had pores of 0.45 μm and was designed to allow macromolecule transport but prevents cells from crossing. Therefore, xenoantigens can escape from the membrane implants and cause an immune reaction. A significantly weaker mononuclear cell infiltration was, however, seen when the membrane barrier was combined with 15‐deoxyspergualin, cyclophosphamide or RS‐61443 treatment but the morphology of the encapsulated ICC was not improved. The best subcapsular, non‐encapsulated graft survival was obtained in animals treated with 15‐deoxyspergualin or cyclophosphamide and the graft insulin content measurements confirmed the morphological data. There was no prolongation of islet‐like cell cluster graft survival under the kidney capsule after ultraviolet‐B irradiation alone (650 J/m² for 90 sec), and no synergistic effect was observed when ultraviolet‐B irradiation was combined with 15‐deoxyspergualin therapy (2.0 mg/kg b.wt.). It is concluded that neither membrane encapsulation with membrane that allow xenoantigen escape from the implants nor ultraviolet‐B irradiation are able to prolong discordant xenograft survival in mice. However, such an effect may be obtained by repeated administration of 15‐deoxyspergualin or cyclophosphamide. 1995 Nordic Pharmacological Society