Ultraviolet light irradiation reduces human islet immunogenicity without altering islet function.
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 beta-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.(ABSTRACT TRUNCATED AT 250 WORDS)
Benhamou
P Y
PY
Diabetes Research Center, UCLA School of Medicine, USA.
Stein
E
E
Hober
C
C
Miyamoto
M
M
Watanabe
Y
Y
Nomura
Y
Y
Watt
P C
PC
Kenmochi
T
T
Brunicardi
F C
FC
Mullen
Y
Y
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000276:immunology* / Q000528:radiation effects*; D016381:Islets of Langerhans Transplantation; D051379:Mice; D008819:Mice, Nude; D013268:Stimulation, Chemical; D014466:Ultraviolet Rays
D007328:Insulin; D005947:Glucose