title: Evolving approaches of hematopoietic stem cell-based therapies to induce tolerance to organ transplants: the long road to tolerance.
abstract: The immunoregulatory properties of hematopoietic stem cells (HSCs) have been recognized for more than 60 years, beginning in 1945, when Owen reported that genetically disparate freemartin cattle sharing a common placenta were red blood cell chimeras. In 1953, Billingham, Brent, and Medawar demonstrated that murine neonatal chimeras prepared by infusion of donor-derived hematopoietic cells exhibited donor-specific tolerance to skin allografts. Various approaches using HSCs in organ transplantation have gradually brought closer to reality the dream of inducing donor-specific tolerance in organ transplant recipients. Several hurdles needed to be overcome, especially the risk of graft-versus-host disease (GVHD), the toxicity of ablative conditioning, and the need for close donor-recipient matching. For wide acceptance, HSC therapy must be safe and reproducible in mismatched donor-recipient combinations. Discoveries in other disciplines have often unexpectedly and synergistically contributed to progress in this area. This review presents a historic perspective of the quest for tolerance in organ transplantation, highlighting current clinical approaches.
authors.affiliation: Comprehensive Transplant Center, Northwestern Memorial Hospital, Chicago, Illinois, USA.
authors.forename: J
authors.initials: J
authors.lastname: Leventhal
authors.forename: J
authors.initials: J
authors.lastname: Miller
authors.forename: M
authors.initials: M
authors.lastname: Abecassis
authors.forename: D J
authors.initials: DJ
authors.lastname: Tollerud
authors.forename: S T
authors.initials: ST
authors.lastname: Ildstad
mesh_terms: D000818:Animals; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods / Q000639:trends*; D006801:Humans; D019172:Transplantation Conditioning / Q000379:methods / Q000639:trends; D023001:Transplantation Tolerance / Q000276:immunology*; D014184:Transplantation, Homologous / Q000379:methods / Q000639:trends; D019737:Transplants / Q000639:trends*