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RA fibroblast-like synoviocytes (RA-FLS) play a central role in initiation and persistence of both synovitis and joint damage 3, 4.

Despite being a systemic disease, the primary clinical manifestations are synovitis and joint destruction. Rheumatoid arthritis (RA) affects approximately 1% of the adult population 1, 2.

Collectively, sfRA-FLS can serve as a an easy-to-obtain source of pathological sublining FLS in RA. Further, sfRA-FLS are comparable to tissue-derived FLS in their capabilities to invade cartilage at implantation sites but also spread tissue destruction to a distant site. We conclude that, sfRA-FLS closely resemble the pathological sublining layer FLS subset in terms of surface protein expression, cytokine production and leukocyte cross-talk potential. In vivo, human sfRA-FLS were cartilage invasive both at ipsilateral and contralateral implantation site. In a co-culture model with autologous PBMC, the ICAM-1 and HLA-DR expression on sfRA-FLS and secretion of IL-1β, IL-6, and MCP-1 increased. SfRA-FLS expressed uniform levels of NFкB-related pathway proteins and secreted several pro-inflammatory cytokines dominated by IL-6 and MCP-1. The in situ activated sfRA-FLS were CD34-, CD45-, Podoplanin+, Thymocyte differentiation antigen-1+. Paired peripheral blood mononuclear cells (PBMC) and sfRA-FLS from patients with RA were obtained and monocultures of sfRA-FLS and autologous co-cultures of sfRA-FLS and PBMC were established. Here we aim to phenotypically and functionally characterize cultured synovial fluid-derived FLS (sfRA-FLS). These cells have primarily been characterized in the RA synovial membrane. Fibroblast-like synoviocytes (FLS) play an important pathological role in persistent inflammatory joint diseases such as rheumatoid arthritis (RA).