Abstract
Allograft rejection is the major cause for failure in clinical islet transplantation for diabetic patients. A reduction of donor islet immunogenicity is potentially a useful approach for altering recipient's immune responses. Studies in animal models have shown the immunomodulatory properties of ultraviolet (UV)-B light that are beneficial for allograft survival. However, there is a narrow window between the doses required for immunomodulation and those toxic to β-cells. In addition, this window varies between one species to another. Our study was designed to determine, in vitro, the UV-B dose for human islets that effectively reduces immunogenicity and maintains islet viability and normal function. Islets were isolated from donor pancreas by collagenase digestion and density gradient centrifugation on Euro-Ficoll. Static incubation and perifusion tests were used to measure glucose-stimulated insulin release. Viability was also assessed by histology and function of UV-irradiated islets transplanted under the renal capsule of athymic mice. The immunogenicity of UV-treated islets was determined in vitro with mixed islet lymphocyte culture using healthy human peripheral blood lymphocytes as responders. At a dose of 300 J/m2, both functional assays detected no impairment of insulin release. At 500 J/m2, a slight decrease of stimulated insulin release was observed only in the perifusion system. At the levels of 600 and 900 J/m2, a clear alteration was observed in both basal and stimulated insulin release. Islets irradiated at 300 J/m2 and transplanted into athymic mice stained strongly for insulin and responded to high glucose challenge in in vivo perfusion performed at two weeks. The immunogenicity of UV-irradiated islets was significantly decreased by 43-81% at 300 J/m2 and 51-70% at 500 J/m2. This effect was still present when tested as late as 9 days after irradiation, but only if islets were irradiated immediately after isolation. We conclude that UV-B irradiation at a dose of 300 J/m2 can effectively reduce immunogenicity of human islets without adverse effects on β-cell survival and function. This low dose UV-B irradiation may be a realistic treatment of human islets prior to transplantation.
| Original language | English |
|---|---|
| Pages (from-to) | 113-120 |
| Number of pages | 8 |
| Journal | Hormone and Metabolic Research |
| Volume | 27 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 01-01-1995 |
| Externally published | Yes |
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All Science Journal Classification (ASJC) codes
- Endocrinology, Diabetes and Metabolism
- Biochemistry
- Endocrinology
- Clinical Biochemistry
- Biochemistry, medical
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Ultraviolet light irradiation reduces human islet immunogenicity without altering islet function. / Benhamou, P. Y.; Stein, E.; Hober, C.; Miyamoto, M.; Watanabe, Y.; Nomura, Y.; Watt, P. C.; Kenmochi, Takashi; Brunicardi, F. C.; Mullen, Y.
In: Hormone and Metabolic Research, Vol. 27, No. 3, 01.01.1995, p. 113-120.Research output: Contribution to journal › Article
TY - JOUR
T1 - Ultraviolet light irradiation reduces human islet immunogenicity without altering islet function
AU - Benhamou, P. Y.
AU - Stein, E.
AU - Hober, C.
AU - Miyamoto, M.
AU - Watanabe, Y.
AU - Nomura, Y.
AU - Watt, P. C.
AU - Kenmochi, Takashi
AU - Brunicardi, F. C.
AU - Mullen, Y.
PY - 1995/1/1
Y1 - 1995/1/1
N2 - Allograft rejection is the major cause for failure in clinical islet transplantation for diabetic patients. A reduction of donor islet immunogenicity is potentially a useful approach for altering recipient's immune responses. Studies in animal models have shown the immunomodulatory properties of ultraviolet (UV)-B light that are beneficial for allograft survival. However, there is a narrow window between the doses required for immunomodulation and those toxic to β-cells. In addition, this window varies between one species to another. Our study was designed to determine, in vitro, the UV-B dose for human islets that effectively reduces immunogenicity and maintains islet viability and normal function. Islets were isolated from donor pancreas by collagenase digestion and density gradient centrifugation on Euro-Ficoll. Static incubation and perifusion tests were used to measure glucose-stimulated insulin release. Viability was also assessed by histology and function of UV-irradiated islets transplanted under the renal capsule of athymic mice. The immunogenicity of UV-treated islets was determined in vitro with mixed islet lymphocyte culture using healthy human peripheral blood lymphocytes as responders. At a dose of 300 J/m2, both functional assays detected no impairment of insulin release. At 500 J/m2, a slight decrease of stimulated insulin release was observed only in the perifusion system. At the levels of 600 and 900 J/m2, a clear alteration was observed in both basal and stimulated insulin release. Islets irradiated at 300 J/m2 and transplanted into athymic mice stained strongly for insulin and responded to high glucose challenge in in vivo perfusion performed at two weeks. The immunogenicity of UV-irradiated islets was significantly decreased by 43-81% at 300 J/m2 and 51-70% at 500 J/m2. This effect was still present when tested as late as 9 days after irradiation, but only if islets were irradiated immediately after isolation. We conclude that UV-B irradiation at a dose of 300 J/m2 can effectively reduce immunogenicity of human islets without adverse effects on β-cell survival and function. This low dose UV-B irradiation may be a realistic treatment of human islets prior to transplantation.
AB - Allograft rejection is the major cause for failure in clinical islet transplantation for diabetic patients. A reduction of donor islet immunogenicity is potentially a useful approach for altering recipient's immune responses. Studies in animal models have shown the immunomodulatory properties of ultraviolet (UV)-B light that are beneficial for allograft survival. However, there is a narrow window between the doses required for immunomodulation and those toxic to β-cells. In addition, this window varies between one species to another. Our study was designed to determine, in vitro, the UV-B dose for human islets that effectively reduces immunogenicity and maintains islet viability and normal function. Islets were isolated from donor pancreas by collagenase digestion and density gradient centrifugation on Euro-Ficoll. Static incubation and perifusion tests were used to measure glucose-stimulated insulin release. Viability was also assessed by histology and function of UV-irradiated islets transplanted under the renal capsule of athymic mice. The immunogenicity of UV-treated islets was determined in vitro with mixed islet lymphocyte culture using healthy human peripheral blood lymphocytes as responders. At a dose of 300 J/m2, both functional assays detected no impairment of insulin release. At 500 J/m2, a slight decrease of stimulated insulin release was observed only in the perifusion system. At the levels of 600 and 900 J/m2, a clear alteration was observed in both basal and stimulated insulin release. Islets irradiated at 300 J/m2 and transplanted into athymic mice stained strongly for insulin and responded to high glucose challenge in in vivo perfusion performed at two weeks. The immunogenicity of UV-irradiated islets was significantly decreased by 43-81% at 300 J/m2 and 51-70% at 500 J/m2. This effect was still present when tested as late as 9 days after irradiation, but only if islets were irradiated immediately after isolation. We conclude that UV-B irradiation at a dose of 300 J/m2 can effectively reduce immunogenicity of human islets without adverse effects on β-cell survival and function. This low dose UV-B irradiation may be a realistic treatment of human islets prior to transplantation.
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U2 - 10.1055/s-2007-979921
DO - 10.1055/s-2007-979921
M3 - Article
C2 - 7607599
AN - SCOPUS:0028910820
VL - 27
SP - 113
EP - 120
JO - Hormone and Metabolic Research
JF - Hormone and Metabolic Research
SN - 0018-5043
IS - 3
ER -