New immunosuppressive strategies for transplantation based on pluripotent stem cell (PSC)-derived immunoregulatory cells

Pluripotent stem cells (PSCs) such as embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs) have the potential to give rise to cells from all three germ layers that can be utilized as new reliable sources in transplantation medicine. However, when allogeneic PSCs are used for transplant generation, an effective immunosuppressive strategy is required to protect transplants from rejection induced by immune responses of recipient to donor alloantigen after transplantation. Cell-based immunosuppressive strategies offer effective, safe and specific methods to inhibit recipient’s immune response against donor transplant and help to avoid side effects accompanied with conventional immunosuppressant drugs. In this context, we hypothesized that allogeneic PSCs-derived transplants can be protected from immune rejection if accompanied with adoptive transfer of immunosuppressive cells generated from the same PSCs. Indeed, we have developed several differentiation protocols to generate immunosuppressive cells such as regulatory T cells (Tregs) or macrophages from PSCs, which showed promising results to prolong same PSCs-derived graft survival. In this review, we introduce new findings related to PSCs-based cellular immunosuppressive therapy and its applications in several transplantation models.