Intra-articular bone marrow mononuclear cell therapy improves arthritis

It looks hopeful and hopefully we will see some long-term studies.
DrO

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 Everett 1 , Bruno C Menarim 1 2 , Sarah H Barrett 3 , Sophie H Bogers 1 , Christopher R Byron 1 , R Scott Pleasant 1 , Stephen R Werre 4 , Linda A Dahlgren 1
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.

PMID: 37876630
PMCID: PMC10591079
DOI: 10.3389/fvets.2023.1256284

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. Copyright © 2023 Everett, Menarim, Barrett, Bogers, Byron, Pleasant, Werre and Dahlgren. Taken from the discussion: Discussion Intra-articular BMNC injection in horses with moderate, naturally-occurring OA was associated with no adverse effects. BMNC was the sole treatment that resulted in decreased objective lameness, which was complemented by a concurrent decrease in joint circumference. The majority of lameness improvement in BMNC-treated horses occurred between 7 and 21 days. There were no significant improvements in lameness or joint circumference in the saline- or triamcinolone-treated groups. Importantly, synovial fluid parameters remained within normal limits for the 21 days following BMNC injection, with a small significant increase in TNCC at day 7; however, TNCC remained within the physiological range. This is the first controlled clinical trial investigating autologous intra-articular BMNC injection for the treatment of horses with naturally-occurring OA and provides objective data supporting a larger clinical trial. BMNC are autologous, readily available without extensive processing, and have the potential for sustained clinical effect and return to joint homeostasis by driving inflammation resolution.