title: Long-term Tolerance Toward Haploidentical Vascularized Composite Allograft Transplantation in a Canine Model Using Bone Marrow or Mobilized Stem Cells.
abstract: BACKGROUND
  The development of safe and reliable protocols for the transplantation of the face and hands may be accomplished with animal modeling of transplantation of vascularized composite allografts (VCA). Previously, we demonstrated that tolerance to a VCA could be achieved after canine recipients were simultaneously given marrow from a dog leukocyte antigen-identical donor. In the present study, we extend those findings across a dog leukocyte antigen mismatched barrier.
  
  
  METHODS
  Eight recipient dogs received total body irradiation (4.5 cGy), hematopoietic cell transplantation (HCT), either marrow (n = 4) or granulocyte-colony stimulating factor mobilized peripheral blood stem cells (n = 4), and a VCA transplant from the HCT donor. Post grafting immunosuppression consisted of mycophenolate mofetil (28 days) and cyclosporine (35 days).
  
  
  RESULTS
  In 4 dogs receiving bone marrow, 1 accepted both its marrow transplant and demonstrated long-term tolerance to the donor VCA (>52 weeks). Three dogs rejected both their marrow transplants and VCA at 5 to 7 weeks posttransplant. Dogs receiving mobilized stem cells all accepted their stem cell transplant and became tolerant to the VCA. However, 3 dogs developed graft-versus-host disease, whereas 1 dog rejected its stem cell graft by week 15 but exhibited long-term tolerance toward its VCA (>90 weeks).
  
  
  CONCLUSIONS
  The data suggest that simultaneous transplantation of mobilized stem cells and a VCA is feasible and leads to tolerance toward the VCA in a haploidentical setting. However, there is a higher rate of donor stem cell engraftment compared with marrow HCT and an increase in the incidence of graft-versus-host disease.
authors.affiliation: 1 Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA. 2 Department of Surgery, University of Washington, Seattle, WA. 3 Department of Medicine, University of Washington, Seattle, WA. 4 Department of Pathology, University of Washington, Seattle, WA. 5 Department of Surgery, University of Colorado, Aurora, CO. 6 Plastic Surgery Service, VA Eastern Colorado Care System, Denver, CO.
authors.forename: Jeff
authors.initials: J
authors.lastname: Chang
authors.forename: Scott S
authors.initials: SS
authors.lastname: Graves
authors.forename: Tiffany
authors.initials: T
authors.lastname: Butts-Miwongtum
authors.forename: George E
authors.initials: GE
authors.lastname: Sale
authors.forename: Rainer
authors.initials: R
authors.lastname: Storb
authors.forename: David Woodbridge
authors.initials: DW
authors.lastname: Mathes
mesh_terms: D000818:Animals; D000941:Antigens / Q000737:chemistry; D001854:Bone Marrow Cells / Q000378:metabolism*; D064595:Composite Tissue Allografts / Q000276:immunology*; D016572:Cyclosporine / Q000494:pharmacology; D004285:Dogs; D006084:Graft Rejection / Q000276:immunology; D006085:Graft Survival; D006086:Graft vs Host Disease; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D018380:Hematopoietic Stem Cell Transplantation; D007165:Immunosuppression Therapy; D007962:Leukocytes / Q000276:immunology; D009173:Mycophenolic Acid / Q000494:pharmacology; D015203:Reproducibility of Results; D016038:Skin Transplantation; D019172:Transplantation Conditioning; D023001:Transplantation Tolerance; D014184:Transplantation, Homologous
chemical_list: D000941:Antigens; D016179:Granulocyte Colony-Stimulating Factor; D016572:Cyclosporine; D009173:Mycophenolic Acid