title: Trafficking of donor-derived bone marrow correlates with chimerism and extension of composite allograft survival across MHC barrier.
abstract: We proposed to evaluate differences between recipient's immune response to vascularized skin and combined vascularized skin/bone allografts, under a 7-day alphabeta-TCR plus cyclosporine (CsA) treatment protocol. Thirty-six transplantations were performed in six groups: group I (isograft control-vascularized skin graft; n=6); group II (isograft control-combined vascularized skin/bone graft; n=6); group III (allograft rejection control group-vascularized skin graft; n=6); group IV (allograft rejection control-combined vascularized skin/bone graft; n=6); group V (allograft treatment-vascularized skin graft; n=6); and group VI (allograft treatment-combined vascularized skin/bone graft; n=6). Isograft transplantations were performed between Lewis rats and allografts were transplanted across the MHC barrier from Brown Norway to Lewis rats. In the allograft treatment group, a combined alphabeta-TCR+CsA protocol was applied for 7 days. All groups were compared clinically, immunologically and histologically. Statistical significance was determined with two-tailed Student's t test. Indefinite graft survival was achieved in the isograft control group (>300 days). Allograft rejection controls rejected within 5 to 9 days posttransplant; chimerism levels were undetectable (<.5%). Allografts under the alphabeta-TCR+CsA protocol had significantly extended survival when skin was combined with bone (61-125 days) compared to vascularized skin allografts (43-61 days). Lymphoid macrochimerism was significantly higher in group VI than group V. Histology confirmed skin and bone viability. Combined vascularized skin/bone allografts had higher and sustained levels of donor-specific chimerism and extended allograft survival.
authors.affiliation: Department of Plastic Surgery, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
authors.forename: S
authors.initials: S
authors.lastname: Ozmen
authors.forename: B G
authors.initials: BG
authors.lastname: Ulusal
authors.forename: A E
authors.initials: AE
authors.lastname: Ulusal
authors.forename: D
authors.initials: D
authors.lastname: Izycki
authors.forename: B
authors.initials: B
authors.lastname: Yoder
authors.forename: M
authors.initials: M
authors.lastname: Siemionow
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000276:immunology*; D016025:Bone Transplantation / Q000276:immunology*; D016572:Cyclosporine / Q000627:therapeutic use; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology; D006085:Graft Survival / Q000276:immunology; D006650:Histocompatibility Testing; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008285:Major Histocompatibility Complex; D023421:Models, Animal; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D016038:Skin Transplantation / Q000276:immunology*; D013234:Stem Cells / Q000276:immunology; D014019:Tissue Donors; D020858:Tissue and Organ Harvesting / Q000379:methods; D018183:Transplantation Chimera; D014184:Transplantation, Homologous / Q000276:immunology; D014185:Transplantation, Isogeneic / Q000276:immunology
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine