title: Adipose tissue-derived mesenchymal stem cells increase skin allograft survival and inhibit Th-17 immune response.
abstract: Adipose tissue-derived mesenchymal stem cells (ADSC) exhibit immunosuppressive capabilities both in vitro and in vivo. Their use for therapy in the transplant field is attractive as they could render the use of immunosuppressive drugs unnecessary. The aim of this study was to investigate the effect of ADSC therapy on prolonging skin allograft survival. Animals that were treated with a single injection of donor allogeneic ADSC one day after transplantation showed an increase in donor skin graft survival by approximately one week. This improvement was associated with preserved histological morphology, an expansion of CD4(+) regulatory T cells (Treg) in draining lymph nodes, as well as heightened IL-10 expression and down-regulated IL-17 expression. In vitro, ADSC inhibit naïve CD4(+) T cell proliferation and constrain Th-1 and Th-17 polarization. In summary, infusion of ADSC one day post-transplantation dramatically increases skin allograft survival by inhibiting the Th-17 pathogenic immune response and enhancing the protective Treg immune response. Finally, these data suggest that ADSC therapy will open new opportunities for promoting drug-free allograft survival in clinical transplantation.
authors.affiliation: Laboratory of Transplantation Immunobiology, Department of Immunology, Institute for Biomedical Sciences, University of São Paulo, São Paulo, Brazil ; Harvard Medical School, Department of Medicine, The Transplant Institute, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America.
authors.forename: Rafael Assumpção
authors.initials: RA
authors.lastname: Larocca
authors.forename: Pedro Manoel
authors.initials: PM
authors.lastname: Moraes-Vieira
authors.forename: Enio José
authors.initials: EJ
authors.lastname: Bassi
authors.forename: Patrícia
authors.initials: P
authors.lastname: Semedo
authors.forename: Danilo Candido
authors.initials: DC
authors.lastname: de Almeida
authors.forename: Marina Burgos
authors.initials: MB
authors.lastname: da Silva
authors.forename: Thomas
authors.initials: T
authors.lastname: Thornley
authors.forename: Alvaro
authors.initials: A
authors.lastname: Pacheco-Silva
authors.forename: Niels Olsen Saraiva
authors.initials: NO
authors.lastname: Câmara
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002450:Cell Communication; D002454:Cell Differentiation; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology; D006085:Graft Survival / Q000235:genetics / Q000276:immunology; D016130:Immunophenotyping; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D010641:Phenotype; D016038:Skin Transplantation; D058504:Th17 Cells / Q000276:immunology*; D014184:Transplantation, Homologous
chemical_list: D016207:Cytokines