Macroencapsulation protects against sensitization after allogeneic islet transplantation in rats

Background. The aim of this study was to evaluate the risks of sensitization by islet grafts encapsulated in a bilaminar immunoprotective membrane. Methods. We studied five groups of Lewis rats: one control group (no islets), two groups that received free islets (200 or 1000 s.c.), and two groups that received encapsulated ones (200 or 1000 s.c.) from DarkAgouti (DA) rats. Four weeks later, abdominal heterotopic DA-heart transplantation was performed on the same recipients. The time-to-heart graft rejection was assessed by the cessation of heart contractions. Rejection was confirmed by histological examinations. Antidonor antibodies were determined by fluorescence activated cell sorter (FACS) analysis. Results. The control animals had a mean heart graft survival of 6.4 days. The free islet groups had significantly shorter heart graft survivals-i.e., 4.8 days (200 islets) and 1.0 day (1000 islets) (P < 0.001)-while those of the encapsulated islet groups were about the same as that of the control group-i.e., 6.4 days (200 islets) and 6.0 days (1000 islets). In the free islet groups, anti-DA antibodies developed in 7/10 (200 islets) and 8/8 (1000 islets) animals after the islet transplantation. In the encapsulated groups, 1/10 (200 islets) and 3/8 (1000 islets) animals developed anti-DA antibodies after these transplantations. All animals had anti-DA antibodies at the time of heart graft rejection. On histological examination all grafts showed various features of rejection. Conclusions. The bilaminar membrane protects against sensitization and prevents accelerated rejection of a subsequent vascularized graft, at least during the first month after the islet transplantation.