Pancreatic Islet Cell Transplantation. Under the guidance of Dr. Amer Rajab, the implementation of a program for clinical transplantation of islet cells into diabetic patients continues to make progress, following the successful isolation of islets from 13 human pancreati. The division has applied to the Food and Drug Administration for approval of this important clinical enterprise. In the meantime, Dr. Rajab and his team continue to refine the techniques to improve sterility and the quality of the islets obtained.
Investigations Funded by the National Institutes of Health. Dr. Ronald Pelletier continues NIH-funded investigations into the immunobiology of graft acceptance and the role of alloantibodies in allograft pathobiology. His recent studies addressing transplantation tolerance suggest that allograft acceptance may evolve through a series of mechanisms involving TGFb and foxP3 regulatory cells. These mechanisms are associated with donor-reactive alloantibodies and pathology within the grafts, and do not lead to true transplantation tolerance, despite the ability to accept donor-matched skin allografts. His ongoing studies of the role of alloantibodies in transplantation reveal that alloantibodies are not necessarily directed at MHC molecules, but are also directed at tissue-associated and tissue-specific molecules. Using new experimental assays for alloantibody detection, his studies have further revealed that some, but not all, of these antibodies are complement-fixing. He also recently demonstrated that grafts undergoing chronic allograft rejection do not exhibit the traditional markers of ischemia, such as HIF-1a. This finding raises the possibility that pathways other than chronic ischemia lead to chronic allograft rejection.
Translational Research in Immunologic Recognition and Post-transplant Outcomes. Dr. Ronald Pelletier continues his translational research (basic, tissue typing, and clinical) investigating the relationship between cellular and humoral donor-specific immunologic recognition and post-transplant outcomes.
Transplantation Immunobiology. Dr. Ginny Bumgardner continues her investigations of transplant immunobiology, using experimental models of pancreatic islet and hepatocyte (liver cell) transplantation. Studies include a research project that focuses on understanding how a novel CD8+ T cell-dependent pathway is activated after transplant, and how it can be suppressed by immunotherapy. This pathway is important, because it can cause transplant tissue damage, either early or late after transplant, and interferes with the induction of transplantation tolerance. Dr. Bumgardner’s laboratory is currently investigating a novel immunosuppressive strategy that successfully suppresses this immunoresistant CD8+ T cell immune pathway and permits long-term allograft survival. Another research project focuses on the effect of oxygen on pancreatic islet viability and how to optimally condition pancreatic islets for transplantation into the liver. These projects are funded by external sponsors, such as the American Diabetes Association, the Roche Organ Transplant Research Foundation, the American Society of Transplant Surgeons, and the National Institutes of Health.