RHEUMATOID ARTHRITIS (RA) MODEL AND ITS APPLICATION IN DRUG TESTING IN-VIVO CELL REMOTE CONTROL: A MECANO-ELECTRO COMPUTATIONAL STUDY AUTOMATED PLATFORM FOR MINIATURIZED CELL CULTIVATION EXPERIMENTS INCLUDING FOURIER-OPTICAL ANALYTICS

Abstract

Rheumatoid arthritis (RA) is a common autoimmune disease that leads to progressive joint destruction. In order to understand the process of rheumatoid cartilage damage, an in vitro model consisting of an inter- active tri-culture of synovial fibroblasts (SFs), LPS-stimulated macrophages and a primary chondrocyte-based tissue engineered construct was established. The tissue engineered construct closely mimicked native cartilage as it was rich in collagen type II and proteoglycans. The results generated revealed that healthy chondrocytes were acti-vated in the presence of SFs and macrophages by displaying aberrant behaviours seen in a disease state. These behaviours include increased apoptosis, decreased gene expression for matrix components such as type II collagen and aggrecan, increased gene expression for tissue-degrading enzymes (MMP-1, -3, -13 and ADAMTS-4, -5), and upreg- ulation of inflammatory mediators gene expression (TNF- a , IL-1 b , IL-6 and IKBKB). Moreover, the inclusion of SFs and macrophages in the model enabled both cell types to more closely replicate their in vivo role in mediating cartilage destruction. This is evidenced by extensive matrix loss detected by immunostaining and biochemical analysis. Subsequent drug treatment with celecoxib indicated that the model was able to respond to the therapeutic effects of this drug by reversing cartilage damage. Taken together, this study showed that the model was able to recapitulate certain pathological features of an RA cartilage. If properly validated, this model has a great potential to be used for screening new therapeutic drugs/strategies, thereby contribut-ing to the improvement of anti-rheumatic treatment.