Newer immunosuppressive drugs in concordant xenografting—Transplantation of hamster heart to rat

Abstract

Recently several promising new immunosuppressive drugs have appeared. In hamster heart to rat transplantation—a commonly used concordant xenograft model—we have investigated the effect of cyclophosphamide, cyclosporine, rapamycin, FK‐506, and leflunomide. When four drugs were given as therapy in combination, we found almost normal morphology of the graft, but over‐immunosuppression was a problem. Leflunomide as a single drug was superior to the other agents. When used in combination leflunomide and cyclosporine offered the best protection of all combinations in our trials, with a mean survival of about 3 months. Further, splenectomy of leflunomide treated xenograft recipients further prolonged graft acceptance. Additional treatment with donor cells from spleen, thymus, and bone marrow did not influence the survival time of the transplanted heart and tolerance was not obtained in any of our studies. The future seems to be a drug combination therapy with decreased side effects due to immunosuppression.

Xenotransplantation

“…With Leflunomide and Cyclosporin, we found many rats surviving with a well-functioning hamster heart for more than 100 days [36]. Earlier attempts showed sporadically good results, such as a rat transplanted with a hamster heart which survived for more than half a year after treatment with drugs, total irradiation and monoclonal antibodies [40].…”

“…Hamster heart transplanted into rat used as model by all five groups is normally rejected in 3-4 days. With newer immunosuppressive drugs, such as Cyclosporin, FK-506, Leflunomide [31], Rapamycin, Brequinar Sodium, and in some laboratories, additional Cyclophosphamide or Cobra Venom Factor, a long transplant survival was seen in laboratories in both America [32,33] and Europe [34][35][36].…”