CO-ENCAPSULATION OF SERTOLI ENRICHED TESTICULAR CELL FRACTIONS FURTHER PROLONGS FISH-TO-MOUSE ISLET XENOGRAFT SURVIVAL1

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Abstract
We previously demonstrated that alginate microencapsulation can prolong fish (tilapia) islet xenograft survival in diabetic animals. However, at present, microencapsulation does not provide complete immune protection to discordant islet xenografts, and long-term graft survival requires supplemental low-dose systemic immunosuppression. In the present study, fish islets were co-encapsulated with Sertoli enriched testicular cell fractions to find out whether this would further prolong fish islet graft survival in diabetic mice. Sertoli enriched testicular cell fractions were enzymatically harvested from adult Balb/c or Wistar-Furth rats. They were cultured and co-encapsulated with fragmented tilapia islets in alginate microcapsules. Encapsulated islets alone or islets co-encapsulated with Sertoli cells were then intraperitoneally transplanted into streptozotocin-diabetic Balb/c mice, and graft survival times were compared. Encapsulated and co-encapsulated islet function was also confirmed in streptozotocin-diabetic athymic nude mice. Co-encapsulation with Sertoli enriched testicular cell fractions further prolonged mean fish islet graft survival time from 21+/-6.7 days (encapsulated islet cells alone) to >46+/-6.3 days (co-encapsulated with syngeneic murine Sertoli cells), without additional systemic immunosuppression. Testicular cells harvested from xenogeneic Wistar-Furth rats produced similar protective results (>46+/-10.9 days). Our results support the theory that Sertoli cells produce local immunosuppressive factors. These factors supplement the immune protective feature of alginate microcapsules in our model. Testicular cell fractions may be an important naturally occurring facilitator in the development of new microencapsulation systems for islet xenotransplantation.