Fetal pancreas transplantation in miniature swine. V. The functional and immunodulatory 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/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-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/m2 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/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.
Benhamou
P Y
PY
Department of Surgery, UCLA School of Medicine 90024-7036, USA.
Kenmochi
T
T
Miyamoto
M
M
Nakagawa
Y
Y
Une
S
S
Stein
E
E
Mullen
Y
Y
D000818:Animals; D002455:Cell Division / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D016332:Fetal Tissue Transplantation / Q000276:immunology*; D005947:Glucose / Q000494:pharmacology; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000528:radiation effects; D007165:Immunosuppression Therapy; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000196:embryology / Q000276:immunology* / Q000528:radiation effects*; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D010179:Pancreas / Q000196:embryology / Q000502:physiology* / Q000528:radiation effects*; D016035:Pancreas Transplantation / Q000276:immunology*; D013268:Stimulation, Chemical; D013552:Swine; D013556:Swine, Miniature; D014466:Ultraviolet Rays
D000949:Histocompatibility Antigens Class II; D007328:Insulin; D005947:Glucose