Isolation and characterization of rheumatoid arthritis synovial fibroblasts from primary culture — primary culture cells markedly differ from fourth-passage cells
OBJECTIVE To establish in SCID.bg mice a model in which joint destruction is initiated by human inflammatory cells from patients with rheumatoid arthritis (RA). METHODS Development of a surgical technique and immunohistologic analysis. RESULTS Initial experiments with single cell suspensions failed because more than 70% of the cells injected intraarticularly left the mouse knee joint within 16 h without causing destruction. This was observed with peripheral blood mononuclear cells, T cell lines reactive to mouse or rat collagen type II, and synovial mononuclear cells. Cell immigration was reduced but not prevented by preactivation with mitogens. In contrast, small tissue implants from human synovial membrane which were transferred by surgical intervention into mouse knee joints remained at the site of injection and could be easily localized within the mouse joint (observation period up to 8 weeks). The human synovial membrane implants induced pannus formation and erosion of cartilage and bone while only a mild and transient synovitis was observed with normal synovial membrane and control tissues like human thymus. The predominant cells at the site of destruction were human (CD68+) and murine (Mac-2+) monocytes/macrophages. CONCLUSION The human/murine SCID arthritis is a useful model for studying pathogenetic aspects of joint destruction as well as effects of new drugs or novel treatment strategies.