Exosomes derived from berberine-treated bone marrow mesenchymal stem cells ameliorate inflammatory arthritis in rats with collagen-induced rheumatoid arthritis

To evaluate the effect of exosomes secreted by berberine-treated bone marrow-derived mesenchymal stem cells (BMSCs) on synovial inflammation in collagen-induced arthritis (CIA) model. Exosomes were isolated from berberine-treated BMSCs (Ber-BMSC-EXs) and untreated BMSCs (BMSC-EXs). CIA rats were developed and treated with Ber-BMSC-EXs or BMSC-EXs. Clinical arthritis index was measured, activation of fibroblast-like synoviocytes (FLSs) were evaluated, and response and frequency of T helper 17 (Th17) and regulatory T (Treg) cells as well as cytokine levels in synovial fluid were determined. Ber-BMSC-EXs (with a superior effect than BMSC-EXs) significantly alleviated RA clinical score and paw inflammation, balanced Th17 and Treg cells’ responses and population, modulated levels of pro-inflammatory and anti-inflammatory cytokines in joint synovial fluid, and inhibited FLS activation in CIA rats. Ber-BMSC-EXs (with a significantly greater effect than BMSC-EXs) could significantly ameliorate synovial joint inflammation and clinical symptoms of arthritis in CIA rats, showing that berberine can reinforce anti-arthritic effects of BMSC-EXs.