title: Immunomodulatory Effects of Different Cellular Therapies of Bone Marrow Origin on Chimerism Induction and Maintenance Across MHC Barriers in a Face Allotransplantation Model.
abstract: Many more patients would benefit from vascularized composite allotransplantation if less toxic and safer immunosuppressive protocols will become available. Tolerance induction protocols with donor cells co-transplantation are one of the promising pathways to reduce maintenance immunosupressive regimens. We investigated the role of donor bone marrow cells (BMC), mesenchymal stromal cells (MSC) and in vivo created chimeric cells (CC) used as supportive therapies in a fully MHC-mismatched rat face transplantation model. Twenty-four fully MHC-mismatched hemiface transplantations were performed between ACI (RT1(a)) donors and Lewis (RT1(l)) recipients under combined seven-day immunosuppressive regimen of anti-αβ-T-cell receptor (TCR) monoclonal antibody and cyclosporin A. We studied four experimental groups-group 1: no cellular therapy; group 2: supportive therapy with BMC; group 3: supportive therapy with MSC; group 4: supportive therapy with CC generated in a primary chimera. We evaluated clinical and histological rejection grades, transplanted cells migration, donor-specific chimerism in the peripheral blood and bone marrow compartments, and CD4(+)/CD25(+) T-cell levels. Face allograft rejection was observed at 26.8 ± 0.6 days post-transplant (PT) in the absence of cellular therapy, at 34.5 ± 1.1 days for group 2, 29.3 ± 0.8 days for group 3, and 30.3 ± 1.38 PT for group 4. The longest survival was observed in allografts supported by co-transplantation of BMC. All support in cellular therapies delayed face allograft rejection by chimerism induction and/or immunomodulatory properties of co-transplanted cells. Survival time was comparable between groups, however, further studies, with different cell dosages, delivery routes and delivery times are required.
authors.affiliation: Department of Plastic Surgery, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Mikael
authors.initials: M
authors.lastname: Hivelin
authors.affiliation: Department of Plastic Surgery, Cleveland Clinic, Cleveland, OH, USA.|L. Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Klimczak
authors.affiliation: Department of Plastic Surgery, Cleveland Clinic, Cleveland, OH, USA.|Department of Orthopedics, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Joanna
authors.initials: J
authors.lastname: Cwykiel
authors.affiliation: Department of Plastic Surgery, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Erhan
authors.initials: E
authors.lastname: Sonmez
authors.affiliation: Department of Plastic Surgery, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Serdar
authors.initials: S
authors.lastname: Nasir
authors.affiliation: Department of Plastic Surgery, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: James
authors.initials: J
authors.lastname: Gatherwright
authors.affiliation: Department of Plastic Surgery, Cleveland Clinic, Cleveland, OH, USA. siemiom@uic.edu.|Department of Orthopedics, University of Illinois at Chicago, Chicago, IL, USA. siemiom@uic.edu.
authors.forename: Maria
authors.initials: M
authors.lastname: Siemionow
mesh_terms: D000818:Animals; D001706:Biopsy; D001853:Bone Marrow / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology* / Q000276:immunology*; D002465:Cell Movement; D002470:Cell Survival; D046528:Chimerism; D005145:Face; D054445:Facial Transplantation / Q000379:methods*; D005434:Flow Cytometry; D006084:Graft Rejection; D006085:Graft Survival; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008285:Major Histocompatibility Complex; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000276:immunology*; D010641:Phenotype; D051381:Rats; D011912:Rats, Inbred ACI; D011917:Rats, Inbred Lew; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D014184:Transplantation, Homologous
chemical_list: D007166:Immunosuppressive Agents; D011948:Receptors, Antigen, T-Cell
keywords: Bone marrow; Chimeric cells; Chimerism and tolerance; Face transplantation; Mesenchymal stromal cells; Vascularized composite allograft/allotransplantation