Mohamed Ezzelarab, MB, ChB

Tolerogenic cell therapy in allo- and xeno-transplantation

Cell therapy is considered a promising approach for induction of antigen-specific tolerance. Dendritic cells (DC) play a key role in the regulation of both adaptive and innate immune responses, in autoimmune diseases and after organ allo-transplantation. Regulatory DC are known to promote central and peripheral tolerance through induction of regulatory T cells and inhibition of memory T cell responses. Regulatory DC are receiving increasing scientific and clinical interest due to their potential use as a cell therapy in order to achieve donor-specific tolerance, and promote graft survival after organ allo-transplantation with minimal immunosuppression. Similarly, mesenchymal stem/stromal cells (MSC) have been shown to ameliorate graft rejection through their regenerative, anti-inflammatory and immunomodulatory properties. Cellular xenografts e.g. islet xenografts have been shown to survive in nonhuman primates, but with intense immunosuppression. In vitro, MSC isolated from genetically-engineered (GE) pigs regulate human and nonhuman primate T cell responses to pig antigens. GE-pig MSC have the potential to improve engraftment of cellular xenografts and regulate recipient T cell responses, in order to promote xenograft survival in nonhuman primates and eventually humans.