XENOTRANSPLANTATION OF ADULT PORCINE ISLETS IN DIABETIC MICE - A STUDY OF UVB IRRADIATION, CRYOPRESERVATION AND IMMUNOSUPPRESSION ON GRAFT-SURVIVAL TIME

The major obstacle for successful xenotransplantation of islets to lar ge animals and human diabetics is the host rejection. To address the r ejection problem, we studied the efficacy of UV-B irradiation, cryopre servation and immunosuppression on the in vivo functional time and imm unogenicity of adult porcine islets (PI) in outbred CD1 mice. Exposure of PI to UV-B irradiation between 300 - 1800 J/M-2 did not affect the cellular viability as assessed by fluorescein diacetate or their dail y insulin secretion in vitro. Fresh PI normalized the blood glucose (B G) of diabetic CD1 mice for 3.1 +/- 0.6 (n = 8, mean +/- SEM) days. Is lets treated with 600 J/M-2 UV-B irradiation or cryopreservation had s imilar graft functional times to fresh islets upon transplantation in diabetic CD1 mice. Immunosuppression with cyclosporin A (CsA), antilym phocyte serum (ALS) and FK506 prolonged the functional time of fresh p ig islets to 7.9 +/- 0.9 (n = 9), 6.2 +/- 1.3 (n = 5) and 24.2 +/- 10. 4 (n = 12) days, respectively. However, additional pretransplant treat ment with either UV-B irradiation or cryopreservation did not further increase the functional time of pig islets in mice immunosuppressed wi th CsA. Furthermore, there was no apparent difference in the frequency of appearance of cytotoxic antibodies and antibody titers in the reci pients of UV-B irradiated or cryopreserved pig islet compared with non -treated islets. The UV-B irradiation and cryopreservation of PI befor e transplantation with the present protocols did not appear to have si gnificant effect on the islet immunogenicity when assessed by in vivo survival duration and anti-donor antibody titer production.