Fetal pancreas transplantation in miniature swine. V. The functional and immunodulatory effects of ultraviolet light on fetal pig islets

Transplantation. 1995 Jun 27;59(12):1660-5.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Division / radiation effects
  • Cell Survival / radiation effects
  • Dose-Response Relationship, Radiation
  • Fetal Tissue Transplantation / immunology*
  • Glucose / pharmacology
  • Histocompatibility Antigens Class II / immunology
  • Histocompatibility Antigens Class II / radiation effects
  • Immunosuppression
  • Insulin / metabolism
  • Insulin Secretion
  • Islets of Langerhans / embryology
  • Islets of Langerhans / immunology*
  • Islets of Langerhans / radiation effects*
  • Islets of Langerhans Transplantation / immunology*
  • Pancreas / embryology
  • Pancreas / physiology*
  • Pancreas / radiation effects*
  • Pancreas Transplantation / immunology*
  • Stimulation, Chemical
  • Swine
  • Swine, Miniature
  • Ultraviolet Rays

Substances

  • Histocompatibility Antigens Class II
  • Insulin
  • Glucose