A major obstacle to stem cell based therapies is the immune response of the patient to stem cell derived tissue, which can be recognized as foreign and attacked by the patient’s immune system. T cells orchestrate immune responses and are “educated” about self versus foreign in an organ called the thymus. It may be possible to educate T cells in a patient to avoid attacking stem cell derived grafts by “re-educating” them in a thymus that contains the same material as the graft. Humanized mouse models have considerable potential as test beds for exploring different therapeutic approaches, including thymic re-education approaches because they allow for human cells to be observed and manipulated experimentally. This proposal aims to refine humanized mouse models to allow for different therapeutic strategies to promote the acceptance of stem cell grafts by a patient’s immune system to be modeled and tested.
This proposal takes advantage of the most recent innovations in microscopic imaging to probe the interactions between developing T cells and their support cells in living 3D tissues. In addition to probing thymic development, in the future these approaches could be further adapted to reveal the cellular events that occur when stem cell derived grafts are accepted or rejected, and to allow for preclinical testing of drugs.
The successful completion of this project will bring us closer to realizing the benefits of stem cell research by providing a viable humanized immune system mouse model for preclinical testing of stem cell-based therapies.