COTRANSPLANTATION OF ALLOGENEIC ISLETS WITH ALLOGENEIC TESTICULAR CELL AGGREGATES ALLOWS LONG-TERM GRAFT-SURVIVAL WITHOUT SYSTEMIC IMMUNOSUPPRESSION

We prepared single-cell suspensions of Lewis rat (RT1(l/l)) testicular cells and cultured these in vitro for 48 h under conditions that prom oted the formation of cellular aggregates. In the absence of systemic immunosuppression, the transplantation of a sufficient quantity of the se aggregates (containing 11 x 10(6) cells, (75% Sertoli cells), toget her with 2,000 purified Lewis rat islets, reversed the diabetic state for >95 days in 100% (5/5) of the chemically diabetic Wistar-Furth (RT 1(u/u)) recipients. Similar grafts consisting of islets alone or islet s plus 50% fewer testicular cell aggregates survived for only 10 days. Functioning composite allografts harvested from normoglycemic animals at similar to 100 days showed healthy beta-cells in close association with Fas ligand-expressing Sertoli cells. Because no gene therapy pro tocol is required, the transplantation of composite grafts consisting of purified human allogeneic islets plus human allogeneic testicular c ell aggregates can be applied in clinical islet transplantation as soo n as it has been proven in a large animal model.