Background: The purpose of this study was to investigate the therapeutic efficacy of intravenously administered\nimmunoselected STRO-3 + mesenchymal precursor cells (MPCs) on clinical scores, joint pathology and cytokine\nproduction in an ovine model of monoarthritis.\nMethods: Monoarthritis was established in 16 adult merino sheep by administration of bovine type II collagen into\nthe left hock joint following initial sensitization to this antigen. After 24 h, sheep were administered either 150\nmillion allogeneic ovine MPCs (n = 8) or saline (n = 8) intravenously (IV). Lameness, joint swelling and pain were\nmonitored and blood samples for leukocytes and cytokine levels were collected at intervals following arthritis\ninduction. Animals were necropsied 14 days after arthritis induction and gross and histopathological evaluations\nwere undertaken on tissues from the arthritic (left) and contralateral (right) joints.\nResults: MPC-treated sheep demonstrated significantly reduced clinical signs of lameness, joint pain and swelling\ncompared with saline controls. They also showed decreased cartilage erosions, synovial stromal cell activation and\nangiogenesis. This was accompanied by decreased infiltration of the synovial tissues by CD4+ lymphocytes and CD14+\nmonocytes/macrophages. Over the 3 days following joint arthropathy induction, the numbers of neutrophils circulating in\nthe blood and plasma concentrations of activin A were significantly reduced in animals administered MPCs.\nConclusions: The results of this study have demonstrated the capacity of IV-administered MPCs to mitigate the clinical\nsigns and some of the inflammatory mediators responsible for joint tissue destruction in a large animal model of\nmonoarthritis.
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