FK 506: an effective immunosuppressant for islet xenotransplantation.

R EPLACING the damaged insulin-producing tissue by transplantation of pancreatic islets is considered the most physiological approach to diabetes treatment and has the potential to prevent the development of chronic complications. Due to the large number of potential diabetic recipients. it would be impossible to obtain sufficient supply of donor organs to fulfill the demands. One solution to resolve donor organ shortage is the use of xenogeneic pancreatic islets. FK 506. a new immunosuppressive agent. is very effective in rat islet allotransplantation across the major histocompatibility (MHC) barrier. 1.1 Use of this agent in islet xenotransplantation has not been studied extensively. The present study was conducted to determine the efficacy of FK 506 on the survival of human islet xenograft in discordant rats. Human islets were isolated from a 12-year-old donor with the automated digestion-filtration methods as described earlier.' Is· lets were then purified with Euro-Collins FicoH gradient in a Cobe 2991 ceil separator. Purified islets were placed in culture medium and transponed from Pittsburgh to Vancouver for xenotransplan· tation. Transplantation and Immunosuppression ~ale ACI rats (Harlan Sprague.Dawley. Indianapolis. Ind) of 200 to 225 g body weight were used as recipients. Human islets stained with dithizone were hand·pickedunder dissection microscope. A total of nine rats were transplanted with 500 human islets each under the left renal capsule. Five transplanted rats received FK 506 (Fujisawa Pharmaceutical Co. Osaka. Japan) treatment at 2 mglkg!d intramuscularly for 2 weeks and then at weekly intervals until they were killed. startinl! immediately after transplantation. The remaining four rats received saline injection.