Fetal pancreas transplantation in miniature swine

V. The functional and immunomodulatory effects of ultraviolet light on fetal pig islets

Pierre Y. Benhamou, Takashi Kenmochi, Masaaki Miyamoto, Yoshi Nakagawa, Satoshi Une, Elizabeth Stein, Yoko Mullen

Research output: Contribution to journalArticle

6 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)1660-1665
Number of pages6
JournalTransplantation
Volume59
Issue number12
DOIs
Publication statusPublished - 27-06-1995
Externally publishedYes

Fingerprint

Miniature Swine
Pancreas Transplantation
Ultraviolet Rays
Swine
Pancreas
Insulin
Animal Models
Glucose
Islets of Langerhans Transplantation
Endocrine Cells
Collagenases
Theophylline
Interferons
Diabetes Mellitus
Lymphocytes
Therapeutics
Growth

All Science Journal Classification (ASJC) codes

  • Transplantation

Cite this

Benhamou, Pierre Y. ; Kenmochi, Takashi ; Miyamoto, Masaaki ; Nakagawa, Yoshi ; Une, Satoshi ; Stein, Elizabeth ; Mullen, Yoko. / Fetal pancreas transplantation in miniature swine : V. The functional and immunomodulatory effects of ultraviolet light on fetal pig islets. In: Transplantation. 1995 ; Vol. 59, No. 12. pp. 1660-1665.
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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 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.",
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Fetal pancreas transplantation in miniature swine : V. The functional and immunomodulatory effects of ultraviolet light on fetal pig islets. / Benhamou, Pierre Y.; Kenmochi, Takashi; Miyamoto, Masaaki; Nakagawa, Yoshi; Une, Satoshi; Stein, Elizabeth; Mullen, Yoko.

In: Transplantation, Vol. 59, No. 12, 27.06.1995, p. 1660-1665.

Research output: Contribution to journalArticle

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T2 - V. The functional and immunomodulatory effects of ultraviolet light on fetal pig islets

AU - Benhamou, Pierre Y.

AU - Kenmochi, Takashi

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AU - Mullen, Yoko

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