Effects of ultraviolet B irradiation on fetal pig islet‐like cell clusters

Abstract

Ultraviolet B (UV-B) irradiation of donor islets has previously been shown to result in the prolongation of their survival when transplanted into rodents. This study examined the in vitro and in vivo effects of UV-B irradiation on fetal pig islet-like cell clusters (ICCs), which like adult islets are being transplanted to reverse diabetes. Under control conditions, fetal pig ICCs were able to stimulate both human and pig peripheral blood mononuclear cells (PBMC) in mixed islet lymphocyte culture (MILC). Exposure of the ICCs to UV-B irradiation significantly reduced their ability to stimulate PBMC of both species in MILC when 600 J/m2 but not lower doses (300 and 400 J/m2) of irradiation were applied. In contrast, all doses of UV-B irradiation were effective in inhibiting the ability of pig and human PBMC to stimulate human PBMC in a mixed lymphocytes culture (MLC). This demonstrates that UV-B irradiation is effective in reducing xeno immunogenicity of pig antigens. A toxic effect of all doses of UV-B irradiation on ICCs was demonstrated in vitro with a reduction in 3H-thymidine incorporation of 57, 71, 64, and 80% at 150, 300, 450, and 600 J/m2, respectively. Toxicity of UV-B irradiation was also demonstrated when treated ICCs were transplanted beneath the renal capsule of SCID mice. The insulin content of the ICCs, 6 weeks after transplantation, was significantly reduced in the 600 J/m2 group (P<0.05). ICCs treated with UV-B irradiation (300 J/m2) in vitro and then transplanted beneath the renal capsule of BALB/c mice were rejected within 2 weeks as were untreated ICCs. Injection of cyclosporine (12.5 mg/ kg/day) into these mice did not alter the results. It is concluded that UV-B irradiation is toxic to fetal pig ICCs and, in low dose, unable to prevent their rejection when transplanted into mice.