title: CD271(+) stromal cells expand in arthritic synovium and exhibit a proinflammatory phenotype.
abstract: BACKGROUND
  CD271(+) stromal cells (SCs) with multipotent stem cell capacity have been identified in synovial tissues, but their functional significance is unknown. We analyzed the distribution of CD271(+) cells in inflammatory synovial tissues as well as their ex vivo immunomodulatory and inflammatory phenotypes.
  
  
  METHODS
  CD271 expression was analyzed by immunohistochemistry in synovial tissues and by flow cytometry in primary adherent synovial cell cultures from rheumatoid arthritis (RA), osteoarthritis (OA), and non-inflammatory control tissues. Isolation of CD271(+) synovial SCs was carried out by magnetic cell sorting. Allogeneic T-cell/SC cocultures were performed to analyze the regulatory capacity of these cells on T-cell proliferation and cytokine production. The production of inflammatory mediators was analyzed in cultures of sorted CD271(+)/(-) SCs. The capacity of CD271(+)/(-) SCs to induce inflammatory cell recruitment in vivo was evaluated in subcutaneous implants in immunodeficient mice.
  
  
  RESULTS
  CD271(+) SC were detected in non-inflammatory as well as in arthritic synovial tissues with a specific perivascular distribution. CD271(+) SC density was increased in RA and OA compared with normal synovial tissues. T-cell proliferation and cytokine synthesis were similarly modified by CD271(+) and CD271(-) SCs. Sorted CD271(+) SCs from OA synovial tissues released significantly more interleukin (IL)-6, matrix metalloproteinase (MMP)-1, and MMP-3 than CD271(-) SCs. In immunodeficient mice, implants of CD271(+) SCs induced significantly higher myeloid cell infiltration than CD271(-) SCs.
  
  
  CONCLUSIONS
  Our results demonstrate that CD271(+) perivascular SCs expand in RA and OA synovial tissues. CD271(+) cells showed enhanced proinflammatory properties ex vivo and in vivo, whereas immunoregulatory properties were equivalent in CD271(+) and CD271(-) SC.
authors.affiliation: Servicio de Reumatología, Instituto de Investigación Hospital 12 de Octubre (i+12), 28041, Madrid, Spain.
authors.forename: Manuel J
authors.initials: MJ
authors.lastname: Del Rey
authors.affiliation: Servicio de Reumatología, Instituto de Investigación Hospital 12 de Octubre (i+12), 28041, Madrid, Spain.
authors.forename: Regina
authors.initials: R
authors.lastname: Faré
authors.affiliation: Servicio de Reumatología, Instituto de Investigación Hospital 12 de Octubre (i+12), 28041, Madrid, Spain.
authors.forename: Alicia
authors.initials: A
authors.lastname: Usategui
authors.affiliation: Unitat d'Artritis, Servei de Reumatologia, Hospital Clínic de Barcelona, Barcelona, Spain.|Institut d'Investigacions Biomèdiques August Pí i Sunyer, Barcelona, Spain.
authors.forename: Juan D
authors.initials: JD
authors.lastname: Cañete
authors.affiliation: Servicio de Cirugía Ortopédica y Traumatología, Hospital 12 de Octubre, Madrid, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Bravo
authors.affiliation: Servicio de Reumatología, Instituto de Investigación Hospital 12 de Octubre (i+12), 28041, Madrid, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Galindo
authors.affiliation: Servicio de Reumatología, Instituto de Investigación Hospital 12 de Octubre (i+12), 28041, Madrid, Spain.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Criado
authors.affiliation: Servicio de Reumatología, Instituto de Investigación Hospital 12 de Octubre (i+12), 28041, Madrid, Spain. jlpablos@h12o.es.
authors.forename: José L
authors.initials: JL
authors.lastname: Pablos
mesh_terms: D000818:Animals; D001168:Arthritis / Q000276:immunology* / Q000473:pathology*; D002478:Cells, Cultured; D005434:Flow Cytometry; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D059630:Mesenchymal Stem Cells / Q000276:immunology* / Q000473:pathology*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010641:Phenotype; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D013583:Synovial Membrane / Q000276:immunology / Q000473:pathology*
chemical_list: C484065:NGFR protein, human; D009419:Nerve Tissue Proteins; D017475:Receptors, Nerve Growth Factor
keywords: Mesenchymal stem cells; Nerve growth factor receptor; Osteoarthritis; Rheumatoid arthritis; Stromal cells; Synovial fibroblasts