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Immunomodulation of fetal pig islet‐like cell clusters by gamma‐irradiation
Author(s) -
Deol Harjit S.,
Tuch Bernard E.
Publication year - 1999
Publication title -
xenotransplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.052
H-Index - 61
eISSN - 1399-3089
pISSN - 0908-665X
DOI - 10.1034/j.1399-3089.1999.00019.x
Subject(s) - in vivo , transplantation , islet , immunogenicity , peripheral blood mononuclear cell , xenotransplantation , in vitro , andrology , fetus , insulin , chemistry , immunology , medicine , immune system , biology , biochemistry , pregnancy , genetics , microbiology and biotechnology
Pretreatment of tissues to reduce their immunogenicity is an attractive option, and exposure of donor islets to gamma‐irradiation has previously been shown to result in their prolonged survival when transplanted into rodents. Fetal pig islet‐like cell clusters (ICCs) are currently under trial as a potential xenogeneic tissue for the treatment of type 1 diabetes. The purpose of this study was to examine in vivo and in vitro the immunomodulatory effects of gamma‐irradiation on ICCs in a xenogeneic situation. The immunogenicity of gamma‐irradiated ICCs was determined in a mixed islet lymphocyte culture (MILC), in which fetal pigs ICCs were able to stimulate human peripheral blood mononuclear cells (PBMCs). Exposure of the ICCs to gamma‐irradiation significantly reduced their ability to stimulate PBMCs in a MILC when 10 Gy but not lower doses of irradiation were applied. However, this effect of gamma‐irradiation was variable and was present only in those experiments in which the stimulation index was relatively low. Gamma‐irradiation was toxic to ICCs in vitro, causing a reduction in the [ 3 H]‐thymidine incorporation of 82–94% at 5–20 Gy. This toxic effect of gamma‐irradiation was also demonstrated in vivo: the insulin content of ICCs beneath the renal capsule in SCID mice treated with 5–20 Gy significantly was reduced ( P < 0.05) 6 weeks after transplantation. Exposure of ICCs to gamma‐irradiation (2.5 Gy) alone in vitro or in combination with injection of cyclosporine (12.5 mg/kg per day) did not prevent the rejection of ICCs transplanted beneath the renal capsule of BALB/c mice. We conclude that gamma‐irradiation is toxic to fetal pig ICCs at a higher dose and at a lower dose, alone or in combination with cyclosporine, and was unable to prolong discordant islet xenograft survival in mice.