title: Human adipose tissue-derived mesenchymal stem cells in rheumatoid arthritis: Regulatory effects on peripheral blood mononuclear cells activation.
abstract: OBJECTIVE
  Mesenchymal stem cells (MSCs) are multipotent adult stem cells with immunomodulatory properties. The mechanisms by which MSCs inhibit the proliferation of pro-inflammatory T cells have not been fully elucidated yet. It is assumed that pro-inflammatory T-cells play an important role in the development of autoimmune diseases. We investigated the potential therapeutic effects of human adipose tissue derived (Ad)-MSCs on the peripheral blood mononuclear cells (PBMCs) of rheumatoid arthritis (RA) patients and healthy individuals, with a particular focus on Th17-associated cytokines.
  
  
  METHODS
  PBMCs from RA patients and healthy donors were co-cultured with Ad-MSCs and HeLa with or without Phytohemagglutinin (PHA). Finally, IL-6, IL-17, IL-21, IL-23 and TGF-β levels were determined by ELISA and quantitative real-time RT-PCR on co-culture supernatants and PBMCs, respectively.
  
  
  RESULTS
  In co-culture interaction, Ad-MSCs inhibited IL-17 secretion by PBMCs compared to unstimulated PBMCs cultured alone. In addition, IL-21 expressions in PBMCs of the patient group, and IL-17 and IL-21 in healthy group were inhibited by Ad-MSCs compared to PBMCs cultured alone. TGF-β expression in healthy individuals remarkably increased in both MSC-treated groups with and without PHA in comparison to PHA-stimulated and -unstimulated PBMCs.
  
  
  CONCLUSIONS
  This study demonstrates that human Ad-MSCs act as key regulators of immune tolerance by inhibiting the inflammation. Therefore, they can be attractive candidates for immunomodulatory cell-based therapy in RA.
authors.affiliation: Department of Immunology and Microbiology, School of Medicine, Jahrom University of Medical Sciences, Jahrom, Iran.
authors.forename: Rasoul
authors.initials: R
authors.lastname: Baharlou
authors.affiliation: Department of Immunology and Microbiology, School of Medicine, Jahrom University of Medical Sciences, Jahrom, Iran. Electronic address: ahvasmehjani@gmail.com.
authors.forename: Abbas
authors.initials: A
authors.lastname: Ahmadi-Vasmehjani
authors.affiliation: Department of Immunology and Microbiology, School of Medicine, Jahrom University of Medical Sciences, Jahrom, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Faraji
authors.affiliation: Department of Immunology and Microbiology, School of Medicine, Jahrom University of Medical Sciences, Jahrom, Iran.
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Atashzar
authors.affiliation: Department of Student Research Committee, School of Medicine, Jahrom University of Medical Sciences, Jahrom, Iran.
authors.forename: Mahshid
authors.initials: M
authors.lastname: Khoubyari
authors.affiliation: Department of Internal Medicine, School of Medicine, Jahrom University of Medical Sciences, Jahrom, Iran.
authors.forename: Salma
authors.initials: S
authors.lastname: Ahi
authors.affiliation: Research Center for Non-Communicable Diseases, School of Medicine, Jahrom University of Medical Sciences, Jahrom, Iran.
authors.forename: Saiedeh
authors.initials: S
authors.lastname: Erfanian
authors.affiliation: Department of Immunology and Microbiology, School of Medicine, Jahrom University of Medical Sciences, Jahrom, Iran.
authors.forename: Shadi-Sadat
authors.initials: SS
authors.lastname: Navabi
mesh_terms: D000273:Adipose Tissue / Q000473:pathology*; D000328:Adult; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000628:therapy; D002454:Cell Differentiation; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007492:Iran; D007963:Leukocytes, Mononuclear / Q000502:physiology*; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D016207:Cytokines
keywords: Adipose tissue-derived mesenchymal stem cells; Inflammation; Peripheral blood mononuclear cells; Rheumatoid arthritis; T helper 17 cells