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Jannette M. Dufour, Ph.D.

Assistant Professor

Investigate the use of immunoprotective Sertoli cells for islet transplantation

Pancreatic islet transplantation is currently being studied as a potential cure for type 1 diabetes; however, this treatment requires chronic immunosuppressive therapy, which can cause adverse side effects. The procedure is further limited by the inadequate supply of human organ donors making it impractical for most patients. Sertoli cells play a critical role in maintaining the immune privileged environment of the testis. Moreover, co-transplantation of Sertoli cells with islets has been shown to reverse diabetes in rodent allogeneic and xenogeneic models without the need for continuous immunosuppression, suggesting Sertoli cells could be used to solve two of the major problems associated with clinical islet transplantation.

Current research is focused on the use of the immunoprotective Sertoli cells as a means to eliminate the need for continual immunosuppressive therapy for islet transplantation and to allow the successful transplantation of an unlimited supply of insulin producing tissue. The second major focus of our research is to identify and characterize immunoprotective factors produced by Sertoli cells as the first step in understanding the mechanisms behind their immunoprotective properties. This research will significantly advance the use of immunoprotective Sertoli cells as a novel solution to the problems associated with islet transplant rejection. One day, this information could allow successful islet transplantation in all persons with type 1 diabetes, including the young juveniles.

Recent Publications

Dufour JM, Rajotte RV, Korbutt GS, Emerlich D. 2003 Harnessing the immunomodulatory properties of Sertoli cells to enable xenotransplantation in type 1 diabetes. Immunological Investigations 32:275-297.

Dufour JM, Rajotte RV, Kin T, Korbutt GS. 2003 Immunoprotection of rat islet xenografts by co-transplantation with Sertoli cells and a single injection of antilymphocyte serum. Transplantation 75:1594-1596.

Dufour JM, Rajotte RV, Seeberger K, Kin T, Korbutt GS. 2003 Long-term survival of neonatal porcine Sertoli cells in non- immunosuppressed rats. Xenotransplantation 10:577-586.

Dufour JM, Hemendinger R, Halberstadt CR, Gores P, Emerich DF, Korbutt GS, Rajotte RV. 2004 Genetically engineered Sertoli cells are able to survive allogeneic transplantation. Gene Therapy 11:694-700.

Dufour JM, Gores P, Hemendinger R, Emerich DF, Halberstadt CR. 2004 Transgenic Sertoli cells as a vehicle for gene therapy. Cell Transplantation 13:1-6.

Kin T, Korbutt GS, Kobayashi T, Dufour JM, Rajotte. 2005 Reversal of diabetes in pancreatectomized pigs after transplantation of neonatal porcine islets. Diabetes 54:1032-1039.

Dufour JM, Hamilton M, Rajotte RV, Korbutt GS. 2005 Neonatal porcine Sertoli cells inhibit human natural antibody mediated lysis. Biology of Reproduction 72:1224-1231.

Dufour JM, Rajotte RV, Zimmerman M, Rezania A, Kin T, Dixon DE, Korbutt GS. 2005 Development of an ectopic site for islet transplantation using biodegradable scaffolds. Tissue Engineering 9/10:1323-1331.

Seeberger K, Dufour JM, Shapiro AMJ, Lakey JRT, Rajotte RV, Korbutt GS. 2006 Expansion of mesenchymal stem cells from human pancreatic ductal epithelium. Laboratory Investigation 86:141-153.

Lord SJ, Sipione S, Motyka B, Ewen C, Shostak I, Rayat GR, Dufour JM, Korbutt GS, Rajotte RV, Bleackley RC. 2006 Identification of a novel human granzyme B inhibitor secreted by cultured Sertoli cells. Journal of Immunology 177:5051-5058.

Dufour JM, Lord SJ, Kin T, Rayat GR, Dixon DE, Bleackley RC, Korbutt GS, Rajotte RV. Comparison of successful and unsuccessful islet/Sertoli cell co-transplant grafts in streptozotocin induced diabetic mice. Cell Transplantation (In Press).

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