FETAL PANCREAS TRANSPLANTATION IN MINIATURE SWINE .5. THE FUNCTIONAL AND IMMUNOMODULATORY EFFECTS OF ULTRAVIOLET-LIGHT ON FETAL PIG ISLETS

We have used the pig as a large animal model for studies of fetal pancreas transplantation. Fetal pig pancreas (FPP) has also been proposed as a potential source of endocrine cells for the treatment of diabetes mellitus, Among the approaches to prevent rejection, the irradiation of donor islets with ultraviolet B light has been used for its immunomodulating properties, Our goal was to study in vitro the effects of UV-B irradiation of FPP on the function and immunogenicity of the tissue, FPP were collagenase-digested and cultured for 1-29 days prior to UV-B irradiation. Static incubation tests were used to measure glucose-theophylline stimulated insulin release, Data obtained at 300 J/m(2) revealed no impairment of insulin release (78% to 129% of controls, P=ns), At 500 J/m(2), a significant reduction of glucose-theophylline stimulated insulin release was observed with 50-60-day-old FPP (35% to 66% of controls, P<0.05), but not with 80-day-old FPP (93% of controls, P=ns), At both doses, prolonged observation in culture did not show any alteration of the growth and proliferation of islet cell clusters, UV-irradiated (300 J/m(2)) adult and fetal pig islet allografts released C-peptide and survived >200 days, The immunogenicity of irradiated tissues was determined in vitro with allogeneic mixed islet-lymphocyte cultures (MILC). Proliferative responses of allogeneic lymphocytes to UV-irradiated FPP were very significantly decreased by 52-91% at both 300 and 500 J/m(2) doses, This effect was observed from 1 to 10 days following UV irradiation and was not modulated by exposure of the tissues to gamma-interferon. We conclude that UVB-irradiation of FPP at a dose of 300 J/m(2) does not alter its endocrine function and growth and is effective in reducing tissue immunogenicity, This treatment may be a useful approach for fetal islet transplantation in large animal models.