In this study, a 3-dimensional synovial membrane model made of either human primary synovial cell suspensions or a mix of primary fibroblast-like synoviocytes and CD14+ mononuclear cells was developed. The composition of the mature micromasses was analysed by immunohistochemical staining and flow cytometry and showed that the outer surface forms a lining layer consisting of fibroblast-like and macrophage-like cells, reflecting the in vivo naïve synovial membrane. To model the affected synovial membrane in rheumatoid arthritis (RA), micromasses were exposed to the pro-inflammatory cytokine tumor necrosis factor alpha (TNF-α), which led to increased pro-inflammatory cytokine expression and production, and to hyperplasia of the membrane. To recreate the synovial membrane in osteoarthritis (OA), the micromasses were exposed to transforming growth factor beta (TGF-β), which led to fibrosis-like changes of the membrane. The macrophages in the micromasses showed phenotypic plasticity, as prolonged TNF-α or TGF-β stimulation strongly reduced the occurrence of CD163+ M2-like macrophages. The study shows the plasticity of the micromasses as a synovial model for studying RA and OA pathology and propose that the synovial lining micromass system can be a good method for drug testing.
A three-dimensional model to study human synovial pathology
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