title: Mesenchymal stem cells from umbilical cord matrix, adipose tissue and bone marrow exhibit different capability to suppress peripheral blood B, natural killer and T cells.
abstract: BACKGROUND
  The ability to self-renew, be easily expanded in vitro and differentiate into different mesenchymal tissues, render mesenchymal stem cells (MSCs) an attractive therapeutic method for degenerative diseases. The subsequent discovery of their immunosuppressive ability encouraged clinical trials in graft-versus-host disease and auto-immune diseases. Despite sharing several immunophenotypic characteristics and functional capabilities, the differences between MSCs arising from different tissues are still unclear and the published data are conflicting.
  
  
  METHODS
  Here, we evaluate the influence of human MSCs derived from umbilical cord matrix (UCM), bone marrow (BM) and adipose tissue (AT), co-cultured with phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (MNC), on T, B and natural killer (NK) cell activation; T and B cells' ability to acquire lymphoblast characteristics; mRNA expression of interleukin-2 (IL-2), forkhead box P3 (FoxP3), T-bet and GATA binding protein 3 (GATA3), on purified T cells, and tumor necrosis factor-alpha (TNF-α), perforin and granzyme B on purified NK cells.
  
  
  RESULTS
  MSCs derived from all three tissues were able to prevent CD4+ and CD8+ T cell activation and acquisition of lymphoblast characteristics and CD56 dim NK cell activation, wherein AT-MSCs showed a stronger inhibitory effect. Moreover, AT-MSCs blocked the T cell activation process in an earlier phase than BM- or UCM-MSCs, yielding a greater proportion of T cells in the non-activated state. Concerning B cells and CD56 bright NK cells, UCM-MSCs did not influence either their activation kinetics or PHA-induced lymphoblast characteristics, conversely to BM- and AT-MSCs which displayed an inhibitory effect. Besides, when co-cultured with PHA-stimulated MNC, MSCs seem to promote Treg and Th1 polarization, estimated by the increased expression of FoxP3 and T-bet mRNA within purified activated T cells, and to reduce TNF-α and perforin production by activated NK cells.
  
  
  CONCLUSIONS
  Overall, UCM-, BM- and AT-derived MSCs hamper T cell, B cell and NK cell-mediated immune response by preventing their acquisition of lymphoblast characteristics, activation and changing the expression profile of proteins with an important role in immune function, except UCM-MSCs showed no inhibitory effect on B cells under these experimental conditions. Despite the similarities between the three types of MSCs evaluated, we detect important differences that should be taken into account when choosing the MSC source for research or therapeutic purposes.
authors.forename: Andreia
authors.initials: A
authors.lastname: Ribeiro
authors.forename: Paula
authors.initials: P
authors.lastname: Laranjeira
authors.forename: Sandrine
authors.initials: S
authors.lastname: Mendes
authors.forename: Isabel
authors.initials: I
authors.lastname: Velada
authors.forename: Cristiana
authors.initials: C
authors.lastname: Leite
authors.forename: Pedro
authors.initials: P
authors.lastname: Andrade
authors.forename: Francisco
authors.initials: F
authors.lastname: Santos
authors.forename: Ana
authors.initials: A
authors.lastname: Henriques
authors.forename: Mário
authors.initials: M
authors.lastname: Grãos
authors.forename: Carla M P
authors.initials: CM
authors.lastname: Cardoso
authors.forename: António
authors.initials: A
authors.lastname: Martinho
authors.forename: Mluísa
authors.initials: M
authors.lastname: Pais
authors.forename: Cláudia Lobato
authors.initials: CL
authors.lastname: da Silva
authors.forename: Joaquim
authors.initials: J
authors.lastname: Cabral
authors.forename: Hélder
authors.initials: H
authors.lastname: Trindade
authors.forename: Artur
authors.initials: A
authors.lastname: Paiva
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D001854:Bone Marrow Cells / Q000166:cytology*; D019002:CD56 Antigen / Q000378:metabolism; D018920:Coculture Techniques; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D053804:Granzymes / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D054353:Perforin / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D014470:Umbilical Cord / Q000166:cytology*
chemical_list: D019002:CD56 Antigen; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D054353:Perforin; D053804:Granzymes