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Presenter: Kevin, Bayrack, Edmonton, Canada
Authors: Kevin Bayrack1, Dana Mihalicz1, Fatemeh Alavi1, Ray V. Rajotte1, Gina R. Rayat1
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Long-term survival of neonatal porcine islet xenografts co-transplanted with Sertoli cells and combined treatment with anti-LFA-1 monoclonal antibody
Kevin Bayrack, Dana Mihalicz, Fatemeh Alavi, Ray V. Rajotte, Gina R. Rayat
Department of Surgery, University of Alberta, Edmonton, AB, Canada
Background: Islet transplantation is a potential therapy for type 1 diabetes. Widespread application of islet transplantation is limited by the shortage of human organ donors and long-term use of immunosuppressive drugs. Neonatal porcine islets (NPI) co-transplanted with neonatal porcine Sertoli cells (SC), combined with short-term anti-LFA-1 monoclonal antibody (mAb) therapy to prevent graft rejection, has thus been proposed. This therapy has yielded long-term graft survival in 74% of mouse recipients (20/27).
Objective: Determine whether long-term survival of NPI is mediated by T regulatory cells (Treg).
Methods: Streptozotocin-induced diabetic C57BL/6 mice received NPI and SC and were treated with anti-LFA-1 mAb. Blood glucose levels were monitored to assess graft function. Immune cells in the islet xenografts and spleen were characterized by immunohistochemistry and flow cytometry, respectively. The presence of islet and SC xenografts were also examined using immunohistochemistry. Cytokines in the graft were detected by RT-PCR analysis. Some mouse recipients were treated with anti-CD25 mAb to determine whether protection of NPI xenografts was mediated by Treg.
Results: The proportion of FoxP3+ Treg was not significantly different between treated B6 mice that rejected or tolerated the xenograft. Low levels of TGF-β1 were detected in the grafts of rejected and tolerant mice, and IL-10 was significantly increased (p < 0.0001) in rejected mice. All of the anti-CD25 mAb treated mice (8/8) remained normoglycemic.
Summary and Conclusion: These data suggest that Treg are not solely responsible for the maintenance of protection generated by co-transplanting NPI and SC combined with short-term anti-LFA-1 mAb therapy.
Keywords: Xenotransplantation, Neonatal Porcine Islets, Sertoli Cells
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