Abstract
Recently, we reported on indefinite islet graft survival in allotransplantation (rat to rat). This was achievable without the use of any immunosuppression by performing transplantation of culture-pretreated (22°C) islets of Langerhans under the renal capsule (r.c.) of chemically induced diabetic recipients. The aim of this study was to test this successful islet modulation technique in a xenogeneic animal model. Six groups of chemically induced diabetic, inbred, C57BL/6J mice received by transplantation either into the liver via the portal vein (i.po.) or under the renal capsule (r.c.) 300–350 either freshly or culture-pretreated (37°C and 22°C) Lewis rat islets without any immunosuppressive therapy. Histology was performed after rejection or post-transplant normoglycaemia (>120 days) for evaluation of the graft. Transplantation of freshly isolated islets resulted in 75% graft rejection 17 days after transplantation. Using culture pretreatment at 37°C, we noted 75% graft rejection 31 days after transplantation. In contrast, culture pretreatment at 22°C resulted in a marked prolongation of xenograft survival, 75% graft rejection occurring 58 days after transplantation, and in two cases there was indefinite graft survival (>120 days). Statistical analysis showed a significant prolongation of xenograft survival after culture pretreatment, with the most beneficial effect appearing after low-temperature culture at 22°C (P<0.05). Interestingly, xenograft survival was markedly prolonged only using the r.c. approach. Statistical comparison revealed a highly significant prolongation using the r.c. as transplantation site compared with i.po. (P<0.001). The prolongation was achievable by combining the r.c. as transplantation site and the culture pretreatment at low temperature (22°C). This effect is similar to the results in allotransplantation, but with a lower rate of indefinite graft survival.
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Jaeger, C., Wöhrle, M., Bretzel, R.G. et al. Effect of transplantation site and culture pretreatment on islet xenograft survival (rat to mouse) in experimental diabetes without immunosuppression of the host. Acta Diabetol 31, 193–197 (1994). https://doi.org/10.1007/BF00571950
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DOI: https://doi.org/10.1007/BF00571950