Cellular Therapeutics-Based Strategies for Inducing Donor-Specific Tolerance to Vascularized Composite Allotransplants

Although vascularized composite allotransplantation (VCA) of the face and extremities has been successfully performed with satisfactory aesthetic and functional outcomes, potentially serious side effects derived from long-term immunosuppression impede broader application of VCA. Induction of donor-specific tolerance to eliminate the requirement of immunosuppression has thus become an ultimate goal that is actively pursued in the field of transplantation. Among the various strategies, great potential has been shown with cellular therapeutics in many animal studies. This chapter summarizes recent progress in the efforts to induce donor-specific tolerance across the full major histocompatibility barrier by strategies based on defined populations of cells, including dendritic cells, mesenchymal stem cells, and regulatory T cells, as well as more recent studies to utilize combinatorial cell-based therapy. Current data and potential influences of cell source (donor versus recipient) are also discussed.