Biotechnology Training Program Seminar
Transplantation of Immune-privileged Sertoli Cells
Jannette Dufour, Texas Tech University Health Sciences Center
Friday, November 6, 2009
12:00 noon
Location: Searle 2407
The testis is an immune privileged site that provides protection for the developing germ cells from an immunological response. Sertoli cells play an important role in maintaining this immune privileged environment, which has led to their use in transplantation. Previously it was shown that Sertoli cells survive and prolong the survival of co-grafted cells when transplanted as allografts or xenografts. However, the mechanism of this protection remains unresolved. Recently, we have found that successful co-transplantation of Sertoli cells with islets was highly dependent on the number of Sertoli cells transplanted and appeared to be associated with the presence of peritubular myoid cells and the formation of tubule-like structures by the Sertoli cells. Cellular infiltrate in successful grafts revealed CD4 T cells and macrophages along the periphery and within the grafts, and very few CD8 T cells. Conversely, examination of unsuccessful grafts, revealed the presence of Sertoli cells arranged randomly and massive CD4, and CD8 T as well as macrophage cell infiltration. Additionally, we have identified several factors involved in inhibition of the complement and apoptotic cascades expressed by Sertoli cells that may be important for survival. In a separate study, we examined the use of Sertoli cells as a vehicle for gene therapy. Sertoli cells transduced with a recombinant adenoviral vector containing modified human insulin cDNA were found to express insulin mRNA and protein. Transplantation of these cells into diabetic SCID mice led to a significant decrease in blood glucose levels demonstrating that Sertoli cells can be modified to produce insulin at levels that normalize blood glucose levels in diabetic mice. Further study of the immune privileged abilities of Sertoli cells may identify novel factors important for testicular immune privilege and improvement of transplant survival.
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