Baboon bone marrow transplantation in humans: application of cross-species disease resistance

Abstract

Xenotransplantation is a newly evolving field. A renewed interest has emerged coincidentally with the shortage of donor organs for transplantation. Bone marrow (BM) chimerism has been suggested as a potential strategy to induce tolerance to xenografts and control the immune response across a species barrier. Bone marrow transplantation (BMTx) displays unique features compared to solid-organ transplantation or transplantation of other cellular grafts. To achieve engraftment of the pluripotent hematopoietic stem cell, which generates all lineages of the hematolymphopoietic system, conditioning of the recipient (usually a combination of irradiation and cytoablative chemotherapy) is required. Once engraftment is achieved, graft function is stable and rejection does not occur, even without immunosuppression. On the other hand, the graft itself is able to generate an immune response against the host, resulting in graft-versus-host disease (GVHD). A newly recognized advantage to xenotransplantation is species-specific disease resistance. In terms of BMTx, important questions arise: Can xenogeneic BM generate a competent immune response across species barriers? Will cross-species GVHD occur? What are the possible applications to humans? This review addresses these questions. Problems emerging from xenogeneic BMTx are summarized and strategies for their solution discussed.