Abstract: Osteoarthritis (OA) can be debilitating and is related to impaired resolution of synovial inflammation. Current treatments offer temporary relief of clinical signs, but have potentially deleterious side effects. Bone marrow mononuclear cells (BMNC) are a rich source of macrophage progenitors that have the ability to reduce OA symptoms in people and inflammation in experimentally-induced synovitis in horses. The objective of this study was to evaluate the ability of intra-articular BMNC therapy to improve clinical signs of naturally occurring equine OA. Horses presenting with clinical and radiographic evidence of moderate OA in a single joint were randomly assigned to 1 of 3 treatment groups: saline (negative control), triamcinolone (positive control), or BMNC (treatment group). Lameness was evaluated subjectively and objectively, joint circumference measured, and synovial fluid collected for cytology and growth factor/cytokine quantification at 0, 7, and 21 days post-injection. Data were analyzed using General Estimating Equations with significance set at < 0.05. There were no adverse effects noted in any treatment group. There was a significant increase in synovial fluid total nucleated cell count in the BMNC-treated group on day 7 (median 440; range 20-1920 cells/uL) compared to day 0. Mononuclear cells were the predominant cell type across treatments at all time points. Joint circumference decreased significantly in the BMNC-treated group from days 7 to 21 and was significantly lower at day 21 in the BMNC-treated group compared to the saline-treated group. Median objective lameness improved significantly in the BMNC group between days 7 and 21. GM-CSF, IL-1ra, IGF-1, and TNF-α were below detectable limits and IL-6, IL-1β, FGF-2 were detectable in a limited number of synovial fluid samples. Inconsistent and limited differences were detected over time and between treatment groups for synovial fluid PGE, SDF-1, MCP-1 and IL-10. Decreased lameness and joint circumference, coupled with a lack of adverse effects following BMNC treatment, support a larger clinical trial using BMNC therapy to treat OA in horses.
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This study investigates the potential use of intra-articular bone marrow mononuclear cell therapy for treating osteoarthritis in horses and reveals promising results in reducing lameness and joint inflammation.
Research Aim
The main objective of the study was to evaluate whether intra-articular treatment with bone marrow mononuclear cells (BMNCs) can alleviate the symptoms of natural osteoarthritis in horses. BMNCs are rich in macrophage progenitors which have been demonstrated to alleviate inflammation and symptoms of osteoarthritis in humans and experimentally-induced synovitis in horses.
Methodology
The study involved horses with clinically observable and radiographic evidence of moderate osteoarthritis in a single joint. They were randomly assigned to three treatment groups: saline (negative control), triamcinolone (positive control), or BMNCs (treatment group).
The horses’ lameness was evaluated both subjectively and objectively, the joint circumference was measured, and synovial fluid was collected for cytology and growth factor/cytokine quantification at different time points: day 0, day 7, and day 21 post-injection.
Results
No adverse effects were observed in any of the treatment groups.
A significant increase in nucleated cells in the synovial fluid was noted in the BMNC-treated group on day 7 compared to day 0, suggesting the BMNCs had entered the affected joint.
The joint circumference notably decreased in the BMNC-treated group from days 7 to 21, indicating a reduction of inflammation.
Improvement in lameness in horses was significantly higher in the BMNC group between days 7 and 21.
Detectable changes in synovial fluid levels of certain cells and substances were inconsistent, with some remaining below detectable limits.
Conclusion
This study indicates that BMNC therapy can potentially be an effective treatment for osteoarthritis in horses, reducing lameness and joint inflammation. The lack of adverse effects further supports the potential use of this treatment.
Thus, a larger clinical trial is required to further evaluate BMNC therapy as a treatment for osteoarthritis in horses. With the growing need for effective treatments for osteoarthritis in horses, these findings may have implications for future treatment strategies.
Cite This Article
APA
Everett JB, Menarim BC, Barrett SH, Bogers SH, Byron CR, Pleasant RS, Werre SR, Dahlgren LA.
(2023).
Intra-articular bone marrow mononuclear cell therapy improves lameness from naturally occurring equine osteoarthritis.
Front Vet Sci, 10, 1256284.
https://doi.org/10.3389/fvets.2023.1256284
Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, United States.
Menarim, Bruno C
Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, United States.
Gluck Equine Research Center, Department of Veterinary Science, Martin-Gatton College of Agriculture, Food and Environment, University of Kentucky, Lexington, KY, United States.
Barrett, Sarah H
Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, United States.
Bogers, Sophie H
Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, United States.
Byron, Christopher R
Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, United States.
Pleasant, R Scott
Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, United States.
Werre, Stephen R
Laboratory for Study Design and Statistical Analysis, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, United States.
Dahlgren, Linda A
Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, United States.
Conflict of Interest Statement
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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