Heart transplant survival in non-human primates : T cell-directed immunosuppressive therapy and regulatory T cells for promotion of heart transplant survival in non-human primates

Heart transplantation significantly enhances the life expectancy of adult patients suffering heart failure, and infants born with malformations of their heart. However, there are many hurdles such as rejection of the transplanted organ, or side effects of the immunosuppressive drugs, that are yet to be overcome. This dissertation focuses on two components that may promote heart transplant survival, and survival of a transplanted organ in general. This Introduction reviews all the important components that are discussed in the thesis; it provides a general overview of the anatomy and function of the heart and the medical relevance of heart transplantation, the importance of non-human primate (NHP) transplant models to carry out the studies for this thesis, and the background of each research topic in relation to its medical relevance

Non-human primate regulatory T cells: Current biology and implications for transplantation

Regulatory T cells (Treg) offer potential for improving long-term outcomes in cell and organ transplantation. The non-human primate model is a valuable resource for addressing issues concerning the transfer of Treg therapy to the clinic. Herein, we discuss the properties of non-human primate Treg and prospects for their evaluation in allotransplantation and xenotransplantation

Technique of endoscopic biopsy of islet allografts transplanted into the gastric submucosal space in pigs

Currently, islet cells are transplanted into the liver via portal vein infusion. One disadvantage of this approach is that it is not possible to adequately biopsy the islets in the liver to assess for rejection. Islet transplantation (Tx) into the gastric submucosal space (GSMS) can be performed endoscopically and has the potential advantage of histological evaluation by endoscopic biopsy. The aim of this study was to determine whether a representative allograft sample could be obtained endoscopically. We performed islet Tx into the GSMS in nonimmunosuppressed pigs using simple endoscopic submucosal injection. Islets were transplanted at four sites. Endoscopic ultrasonography and biopsy of the transplanted islets at two sites by modified endoscopic submucosal dissection were carried out successfully in all pigs 5 days after islet Tx. Tissue obtained at both biopsy and necropsy (including full-thickness sections of the gastric wall around the sites of the remaining islets and biopsies) were examined by histology and immunohistochemistry to confirm the presence of the islet grafts and any features of rejection. Representative allograft sampling was successfully obtained from all biopsy sites. All biopsies included islets with insulin-positive staining. There was significant CD3+ and CD68+ cell infiltration in the islet masses obtained at biopsy and from sections taken at necropsy, with similar histopathological features. Endoscopic biopsy of islet allografts in the GSMS is feasible, provides accurate histopathological data, and would provide a significant advance if translated into clinical practice