title: Immunomodulatory effects of bone marrow-derived mesenchymal stem cells in a swine hemi-facial allotransplantation model.
abstract: BACKGROUND
  In this study, we investigated whether the infusion of bone marrow-derived mesenchymal stem cells (MSCs), combined with transient immunosuppressant treatment, could suppress allograft rejection and modulate T-cell regulation in a swine orthotopic hemi-facial composite tissue allotransplantation (CTA) model.
  
  
  RESULTS
  Outbred miniature swine underwent hemi-facial allotransplantation (day 0). Group-I (n = 5) consisted of untreated control animals. Group-II (n = 3) animals received MSCs alone (given on days -1, +1, +3, +7, +14, and +21). Group-III (n = 3) animals received CsA (days 0 to +28). Group-IV (n = 5) animals received CsA (days 0 to +28) and MSCs (days -1, +1, +3, +7, +14, and +21). The transplanted face tissue was observed daily for signs of rejection. Biopsies of donor tissues and recipient blood sample were obtained at specified predetermined times (per 2 weeks post-transplant) or at the time of clinically evident rejection. Our results indicated that the MSC-CsA group had significantly prolonged allograft survival compared to the other groups (P<0.001). Histological examination of the MSC-CsA group displayed the lowest degree of rejection in alloskin and lymphoid gland tissues. TNF-α expression in circulating blood revealed significant suppression in the MSC and MSC-CsA treatment groups, as compared to that in controls. IHC staining showed CD45 and IL-6 expression were significantly decreased in MSC-CsA treatment groups compared to controls. The number of CD4+/CD25+ regulatory T-cells and IL-10 expressions in the circulating blood significantly increased in the MSC-CsA group compared to the other groups. IHC staining of alloskin tissue biopsies revealed a significant increase in the numbers of foxp3(+)T-cells and TGF-β1 positive cells in the MSC-CsA group compared to the other groups.
  
  
  CONCLUSIONS
  These results demonstrate that MSCs significantly prolong hemifacial CTA survival. Our data indicate the MSCs did not only suppress inflammation and acute rejection of CTA, but also modulate T-cell regulation and related cytokines expression.
authors.affiliation: Center for Composite Tissue Allotransplantation, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Yur-Ren
authors.initials: YR
authors.lastname: Kuo
authors.forename: Chien-Chang
authors.initials: CC
authors.lastname: Chen
authors.forename: Shigeru
authors.initials: S
authors.lastname: Goto
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Huang
authors.forename: Chun-Ting
authors.initials: CT
authors.lastname: Wang
authors.forename: Chia-Chun
authors.initials: CC
authors.lastname: Tsai
authors.forename: Chao-Long
authors.initials: CL
authors.lastname: Chen
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology*; D016572:Cyclosporine; D004797:Enzyme-Linked Immunosorbent Assay; D054445:Facial Transplantation; D005434:Flow Cytometry; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D007150:Immunohistochemistry; D007155:Immunologic Factors / Q000494:pharmacology*; D053208:Kaplan-Meier Estimate; D045164:Mesenchymal Stem Cell Transplantation; D013552:Swine; D013556:Swine, Miniature; D013601:T-Lymphocytes / Q000276:immunology*; D014184:Transplantation, Homologous / Q000276:immunology*
chemical_list: D007155:Immunologic Factors; D016572:Cyclosporine