Fetal pancreas transplantation in miniature swine: V. 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 immunogenic-ity 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-theo-phylline stimulated insulin release. Data obtained at 300 J/m2 revealed no impairment of insulin release (78% to 129% of controls, P=ns). At 500 J/m², 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/m²) 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-lym-phocyte cultures (MILC). Proliferative responses of allogeneic lymphocytes to UV-irradiated FPP were very significantly decreased by 52-91% at both 300 and 500 J/m² doses. This effect was observed from 1 to 10 days following UV irradiation and was not modulated by exposure of the tissues to γ-interferon. We conclude that UVB-irradiation of FPP at a dose of 300 J/m² 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.