The Role of Macrophages in Sertoli Cell Transplant Survival Without the Use of Immunosuppressive Drugs

Abstract

INTRODUCTION: Islet transplantation is an innovative method to treat diabetes; however, the immunosuppressive drugs necessary to prevent transplant rejection make patients susceptible to infections, cancer, and are even detrimental to the transplanted islet function. Sertoli cells (SC) are immune-privileged testicular cells that have potential as an alternative to immunosuppressive therapy, because they have been shown to protect co-transplanted islets without the use of chronic immunosuppressive drugs. However, the mechanisms by which SC extend graft survival remain unknown. Because the successful SC/islet co-grafts contain macrophages, we examined the role of macrophages in SC transplant survival. METHODS: C57BL6 SC or MSC-1 cells (rejecting control mouse SC line) (donors) were transplanted under the left kidney capsule of control or macrophage-depleted (MOKO) BALB/c mice (recipients). Macrophages were depleted using chlorate liposome injections. Grafts were collected at day 20 post-transplantation and analyzed for cell survival by immunohistochemistry (IHC) and macrophage depletion by IHC and flow cytometry. RESULTS: Macrophages were present in control recipients and confirmed depleted in MOKO recipients. In control recipients, 100% of the SC grafts survived, but 100% of the MSC-1 grafts were rejected. In MOKO recipients, SC grafts exhibited 100% survival. Surprisingly, 56% of MSC-1 grafts survived, which is especially interesting because normally they are rejected. CONCLUSION: These results indicate that macrophages are not required for SC survival; however, macrophages may be involved in graft rejection. Understanding the role of macrophages in transplantation could lead to improved graft survival and increased viability of islet transplants.