title: Modulation of immune response and T-cell regulation by donor adipose-derived stem cells in a rodent hind-limb allotransplant model.
abstract: BACKGROUND
  In this study, the authors investigated whether donor adipose-derived stem cells have immunomodulatory effects, such as regulation of T cells, modulation of related cytokines, and prolongation of composite tissue allotransplantation survival, in a rodent hind-limb model.
  
  
  METHODS
  Adipose-derived stem cells were obtained from donor adipose tissue and co-cultured with CD3 T cells from allogenic splenocytes for in vitro studies. Orthotopic hind-limb allotransplants were performed from Brown Norway to Lewis rats (day 0). Group 1 (control group) did not receive any treatment. Group 2 received cyclosporin A on days 0 to 20. Group 3 received antilymphocyte serum (day -4 and day 1) and cyclosporin A (days 0 to 20). Group 4 received cyclosporin A (days 0 to 20), antilymphocyte serum (day -4 and day 1), and adipose-derived stem cells (2 × 10 cells/time administered intravenously on days 7, 14, and 21).
  
  
  RESULTS
  Adipose-derived stem cells exert immunomodulatory effects including suppressing T-cell proliferation and increasing CD4/CD25/Foxp3 regulatory T cells in vitro. The in vivo study revealed that, compared with untreated control, rats administered adipose-derived stem cells along with transient antilymphocyte serum and cyclosporin A treatment had significantly prolonged allotransplant survival (p < 0.001), decreased allotissue rejection, significantly elevated donor cell chimerism, and increased CD4/CD25/Foxp3 regulatory T cells in peripheral blood and alloskin tissue with up-regulation of transforming growth factor-β and interleukin-10 levels.
  
  
  CONCLUSIONS
  In combination with transient immunosuppression, adipose-derived stem cells modulate the immune system and significantly prolong allotransplant survival. The underlying mechanisms include changes in antiinflammatory cytokine expression and T-cell functions.
authors.affiliation: Kaohsiung, Taiwan From the Department of Plastic and Reconstructive Surgery, Medical Research, and the Liver Transplantation Program and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine.
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: I-Te
authors.initials: IT
authors.lastname: Lee
authors.forename: Chong-Wei
authors.initials: CW
authors.lastname: Huang
authors.forename: Chia-Chun
authors.initials: CC
authors.lastname: Tsai
authors.forename: Chun-Ting
authors.initials: CT
authors.lastname: Wang
authors.forename: Chao-Long
authors.initials: CL
authors.lastname: Chen
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D000961:Antilymphocyte Serum / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology; D006085:Graft Survival / Q000276:immunology; D006614:Hindlimb / Q000637:transplantation*; D056747:Immunomodulation / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D013234:Stem Cells / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014019:Tissue Donors; D014181:Transplantation Immunology / Q000276:immunology*; D014184:Transplantation, Homologous
chemical_list: D000961:Antilymphocyte Serum; D016207:Cytokines; D007166:Immunosuppressive Agents; D016572:Cyclosporine