PANCREATIC-ISLET XENOGRAFTS AT 2 DIFFERENT TRANSPLANTATION SITES (RENAL SUBCAPSULAR VERSUS INTRAPORTAL) - COMPARISON OF GRAFT-SURVIVAL AND MORPHOLOGY

Our primary objective in this study was to determine the effect of two different transplantation sites (renal capsule vs. portal vein) on is let xenograft survival and graft morphology. 59 chemically induced dia betic C57BL/6J mice were transplanted either intraportally (n = 30) or under the left renal capsule (n = 29) receiving 300-350 either freshl y isolated or culture pretreated (37 degrees C or 22 degrees C) Lewis rat islets without any immunosuppressive therapy. Histology was perfor med by immunohistochemical staining to examine the morphologic pattern after rejection or after post-transplant normoglycemia for more than 120 days. Life table analysis revealed a significant (p < 0.001) prolo ngation of xenograft survival using the renal capsule as transplantati on site. 75% graft rejection occurred 56 days after transplantation wh en the renal capsule was used, compared to 19.5 days intraportal. The intriguing finding was that graft morphology was different depending o n the transplantation site. After transplantation under the renal caps ule we observed predominantly a more periinsular infiltration with foc al aggregates of mononuclear cells at the periphery of the graft. This pattern was more consistent with a non-destructive type of insulitis. In contrast, we found direct infiltration of the transplanted islets following intraportal transplantation reflecting a more destructive ty pe of insulitis. In summary, we could demonstrate a significant prolon gation of islet xenograft survival by using the renal capsule as trans plantation site in contrast to intraportal transplantation. The morpho logical pattern possibly indicates two different mechanisms of rejecti on depending on the transplantation site.