Intra-articular bone marrow mononuclear cell therapy improves lameness from naturally occurring equine osteoarthritis

J Blake Everett; Bruno C Menarim; Sarah H Barrett; Sophie H Bogers; Christopher R Byron; R Scott Pleasant; Stephen R Werre; Linda A Dahlgren

doi:10.3389/fvets.2023.1256284

Intra-articular bone marrow mononuclear cell therapy improves lameness from naturally occurring equine osteoarthritis

Front Vet Sci. 2023 Oct 9:10:1256284. doi: 10.3389/fvets.2023.1256284. eCollection 2023.

Authors

J Blake Everett¹, Bruno C Menarim^{1

2}, Sarah H Barrett³, Sophie H Bogers¹, Christopher R Byron¹, R Scott Pleasant¹, Stephen R Werre⁴, Linda A Dahlgren¹

Affiliations

¹ Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, United States.
² Gluck Equine Research Center, Department of Veterinary Science, Martin-Gatton College of Agriculture, Food and Environment, University of Kentucky, Lexington, KY, United States.
³ Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, United States.
⁴ Laboratory for Study Design and Statistical Analysis, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, United States.

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 p < 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 PGE₂, 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.

Keywords: BMNC; inflammation; macrophage; osteoarthritis; synovitis.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was funded by the Virginia Veterinary Medical Veterinary Memorial Fund and the Virginia Horse Industry Board. Salary support provided by the VMCVM (JE and BM) and the Virginia Tech Regenerative Medicine Interdisciplinary Graduate Education Program (BM).