It is not known whether stem-cell derived beta cells for transplantation will be derived from autologous (genetically identical) or allogeneic (genetically dissimilar) sources. Allogeneic cells will be more readily made into an “off-the-shelf” product, whereas autologous would be more “bespoke”. An autologous source will mean that allogeneic transplant rejection will not occur but, without immunosuppression, autoimmunity is likely to recur targeting the transplanted beta cells.
The aim of this project is to understand the minimal amount of immunotherapy needed to prevent recurrence of autoimmune diabetes in the transplanted beta cells. Diabetic NOD mice will be transplanted with syngeneic/autologous islets and will be treated at the same time with previously tested diabetes therapies. Flow cytometry and genomic testing of the transplanted beta cells and infiltrating T cells will be carried out. In particular, we will use technology that allows detection and analysis of antigen-specific T cells.