Acceptance of Allogeneic Cell Transplants without Systemic Immune Suppression

Cell-based therapies hold great promise for the future of modern medicine. A large number of injuries and diseases that are currently not possible to cure or effectively treat could benefit from therapeutic approaches where healthy cells are transplanted into the disease/injury sites. However, before stem cell-based therapies can become a reality, several major obstacles need to be overcome. One of the most pressing is the rejection of allogeneic transplants. Although patient-derived induced Pluripotent Stem Cells (iPSCs) may offer an appealing solution, the derivation, expansion and quality control needed for application in clinical settings is prohibitively expensive and time-consuming. This thesis describes the creation of pluripotent stem cell lines that are accepted as allografts without the need for systemic immune suppression. We genetically altered murine Embryonic Stem Cells (mESCs) to express a set of eight immune-modulatory genes at high levels. Transplantation of these cells into allogeneic hosts resulted in the successful formation of teratomas. Most importantly, this immunologic acceptance was achieved without the administration of immune-suppressive drugs. We envision that this approach will allow the same cell line to be used for transplantation into any individual. Rigorous testing and quality control would be cost-effective and cells could be made available as “off the shelf” products.Ph.D