Severe joint synovial inflammation with cartilage loss and bony erosions, characteristic of human RA, occurs in sheep injected with collagen. In a pilot study, significant numbers of allogeneic MPCs were detected in involved joints or lymph nodes of arthritic sheep at 24 hours after a single intravenous injection, but not in normal sheep, indicating that MPCs selectively migrate to sites of immune-mediated inflammation.A randomized, placebo-controlled study was next performed in 30 sheep with established collagen-induced arthritis, comparing a single intravenous injection of allogeneic MPCs at one of three doses (0.3, 1 and 2 million MPCs/kg) to saline. Thirty days later, joint synovial tissues from arthritic sheep were examined. In comparison with saline treated controls, synovial tissue from arthritic sheep receiving a single intravenous injection of 2 million MPCs/kg showed 88% mean reduction in IL-6 levels (p=0.029), 83% mean reduction in TNF-alpha levels (p=0.049), 53% mean reduction in IL-17 levels (p=0.005), and 52% mean reduction in infiltrating monocytes/macrophages (p=0.009). MPC-treated animals had a 31% mean reduction in histopathology severity scores compared with controls (p=0.025). Intermediate effects were seen with 1 million MPCs/kg, and the lowest MPC dose was least effective.
Rheumatoid Arthritis New Major Clinical Target After Mesoblast Obtains Positive Results In Inflammatory Arthritis
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