title: Mixed allogeneic chimerism and tolerance to composite tissue allografts.
abstract: The development of effective immunosuppressive drugs has made solid organ allotransplantation the preferred approach for treatment of end-organ failure. The benefits of these immunosuppressants outweigh their risks in preventing rejection of lifesaving solid-organ allografts. On the contrary, composite tissue allotransplants are non-lifesaving and whether the risks of immunosuppressants justify their benefits is a subject of debate. Hence, composite tissue allografts (CTA) have not enjoyed widespread clinical application for reconstruction of large tissue defects. Therefore, a method of preventing rejection that would eliminate the need for toxic immunosuppressants is of particular importance in CTA. Bone marrow transplantation (BMT) to establish mixed chimerism induces tolerance to a variety of allografts in animal models. This article reviews mixed chimerism-based tolerance protocols. Their limitations and their relevance to CTA are discussed, highlighting some unique characteristics (high antigenicity and the presence of active bone marrow) that make CTAs different from solid organ allografts.
authors.affiliation: Plastic Surgery Research, Department of Surgery, University of Louisville, Louisville, Kentucky, USA.
authors.forename: K A
authors.initials: KA
authors.lastname: Prabhune
authors.forename: V S
authors.initials: VS
authors.lastname: Gorantla
authors.forename: C
authors.initials: C
authors.lastname: Maldonado
authors.forename: G
authors.initials: G
authors.lastname: Perez-Abadia
authors.forename: J H
authors.initials: JH
authors.lastname: Barker
authors.forename: S T
authors.initials: ST
authors.lastname: Ildstad
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D006084:Graft Rejection / Q000517:prevention & control*; D006086:Graft vs Host Disease / Q000517:prevention & control; D006801:Humans; D007108:Immune Tolerance; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016378:Tissue Transplantation; D018183:Transplantation Chimera; D014184:Transplantation, Homologous
chemical_list: D007166:Immunosuppressive Agents