Simultaneous donor bone marrow and cardiac transplantation: Can tolerance be induced with the development of chimerism?

Mixed bone marrow chimerism (mixed chimerism) is defined by the coexistence of two genetically different bone marrow stem cells in an individual. The chimeric immune system recognizes donor antigen as self, yet is capable of mounting a normal response to third-party antigens. In animal models, mixed chimerism confers donor-specific tolerance for solid-organ and cellular grafts: tissue from the bone marrow donor is permanently accepted by mixed chimeras in the absence of conventional immunosuppressive agents. Clinical application of mixed chimerism to induce transplantation tolerance requires novel approaches to safely and reliably achieve engraftment of donor bone marrow in transplant recipients. Recent advances offer potential solutions to these obstacles and suggest that the application of mixed chimerism to induce tolerance to transplanted organs may soon be a clinical reality.