Autologous Bone Marrow Mononuclear Cells Modulate Joint Homeostasis in an Equine in Vivo Model of Synovitis

Osteoarthritis (OA) is characterized by macrophage‐driven synovitis. Macrophages promote synovial health but become inflammatory when their regulatory functions are overwhelmed. Bone marrow mononuclear cells (BMNCs) are a rich source of macrophage progenitors used for treating chronic inflammation and produce essential molecules for cartilage metabolism. This study investigated the response to autologous BMNC injection in normal and inflamed joints. Synovitis was induced in both radiocarpal joints of 6 horses. After 8 h, 1 inflamed radiocarpal and 1 normal tarsocrural joint received BMNC injection. Contralateral joints were injected with saline. Synovial fluid was collected at 24, 96, and 144 h for cytology, cytokine quantification, and flow cytometry. At 144 h, horses were euthanatized, joints were evaluated, and synovium was harvested for histology and immunohistochemistry. Four days after BMNC treatment, inflamed joints had 24% higher macrophage counts with 10% more IL‐10+ cells than saline‐treated controls. BMNC‐treated joints showed gross and analytical improvements in synovial fluid and synovial membrane, with increasing regulatory macrophages and synovial fluid IL‐10 concentrations compared with saline‐treated controls. BMNC‐treated joints were comparable to healthy joints histologically, which remained abnormal in saline‐treated controls. Autologous BMNCs are readily available, regulate synovitis through macrophage‐associated effects, and can benefit thousands of patients with OA.—Menarim, B. C., Gillis, K.H., Oliver, A., Mason, C., Ngo, Y., Werre, S.R., Barrett, S.H., Luo, X., Byron, C.R., Dahlgren, L. A. Autologous bone marrow mononuclear cells modulate joint homeostasis in an equine in vivo model of synovitis. FASEB J. 33, 14337‐14353 (2019). www.fasebj.org