Cotransplantation with xenogenetic neonatal porcine sertoli cells significantly prolongs islet allograft survival in nonimmunosuppressive rats

Abstract

Background: In addition to possessing immune privileged properties, Sertoli cells are known to actively suppress responses to cotransplanted cells. An important question is whether this "bystander suppression" is limited to cells of the same origin as the Sertoli cells or whether suppression extends to unrelated cells.

Methods: Neonatal porcine Sertoli cells (NPSCs) were transplanted with allogeneic islets (Sprague-Dawley rat) into immune competent Wistar rats subsequent to induction of diabetes by alloxan administration.

Results: Although allogeneic islets alone had a mean survival time of 5.67+/-0.94 days, islets cotransplanted with 1.5 x 10 xenogeneic NPSCs displayed a survival of 8.33+/-0.58 days. Increasing the concentration of NPSCs to 1.0 x10 yielded a further increase in survival to 16.33+/-1.53 days. Augmented islet survival was associated with reduced lymphocytic infiltrate and elevated numbers of Sox9 positive cells. Mechanistically, it seemed that Fas ligand was not involved in prolongation of survival because in contrast to adult Sertoli cells, NPSCs lacked expression of this gene.

Conclusions: These data suggest that xenogeneic Sertoli cells exert a global immune suppressive effect that extends across species barriers in a stringent model of alloimmune rejection. The combination of NPSCs with other immune modulatory regimes may yield novel approaches toward prevention of allo-islet transplant rejection.