EFFECT OF TRANSPLANTATION SITE AND CULTURE PRETREATMENT ON ISLET XENOGRAFT SURVIVAL (RAT TO MOUSE) IN EXPERIMENTAL DIABETES WITHOUT IMMUNOSUPPRESSION OF THE HOST

Recently, we reported on indefinite islet graft survival in allotransp lantation (rat to rat). This was achievable without the use of any imm unosuppression by performing transplantation of culture-pretreated (22 degrees C) islets of Langerhans under the renal capsule (r.c.) of che mically induced diabetic recipients. The aim of this study was to test this successful islet modulation technique in a xenogeneic animal mod el. Six groups of chemically induced diabetic, inbred, C57BL/6J mice r eceived by transplantation either into the liver via the portal vein ( i.po.) or under the renal capsule (r.c.) 300-350 either freshly or cul ture-pretreated (37 degrees C and 22 degrees C) Lewis rat islets witho ut any immunosuppressive therapy. Histology was performed after reject ion or post-transplant normoglycaemia (>120 days) for evaluation of th e graft. Transplantation of freshly isolated islets resulted in 75% gr aft rejection 17 days after transplantation. Using culture pretreatmen t at 37 degrees C, we noted 75% graft rejection 31 days after transpla ntation. In contrast, culture pretreatment at 22 degrees C resulted in a marked prolongation of xenograft survival, 75% graft rejection occu rring 58 days after transplantation, and in two cases there was indefi nite graft survival (>120 days). Statistical analysis showed a signifi cant prolongation of xenograft survival after culture pretreatment, wi th the most beneficial effect appearing after low-temperature culture at 22 degrees C (P<0.05). Interestingly, xenograft survival was marked ly prolonged only using the r.c. approach. Statistical comparison reve aled a highly significant prolongation using the r.c. as transplantati on site compared with i.po. (P<0.001). The prolongation was achievable by combining the r.c. as transplantation site and the culture pretrea tment at low temperature (22 degrees C). This effect is similar to the results in allotransplantation, but with a lower rate of indefinite g raft survival.