CD271(+) stromal cells expand in arthritic synovium and exhibit a proinflammatory phenotype

Arthritis Res Ther. 2016 Mar 15;18:66. doi: 10.1186/s13075-016-0966-5.


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.

Keywords: Mesenchymal stem cells; Nerve growth factor receptor; Osteoarthritis; Rheumatoid arthritis; Stromal cells; Synovial fibroblasts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis / immunology*
  • Arthritis / pathology*
  • Cells, Cultured
  • Flow Cytometry
  • Heterografts
  • Humans
  • Immunohistochemistry
  • Inflammation / immunology
  • Inflammation / pathology
  • Mesenchymal Stem Cells / immunology*
  • Mesenchymal Stem Cells / pathology*
  • Mice
  • Nerve Tissue Proteins / metabolism
  • Phenotype
  • Receptors, Nerve Growth Factor / metabolism
  • Synovial Membrane / immunology
  • Synovial Membrane / pathology*


  • NGFR protein, human
  • Nerve Tissue Proteins
  • Receptors, Nerve Growth Factor