Cord blood mesenchymal stromal cells combined with hyaluronic acid show symptom-modifying and potential disease-modifying effects in an equine osteoarthritis fetlock chip model.

INTRODUCTION: Osteoarthritis (OA) is a major cause of lameness in horses, and current therapies largely address clinical signs rather than disease progression. Mesenchymal stromal cells (MSCs) have shown promise as disease-modifying biologics, but their effects on joint structure and immunologic phenotype remain incompletely characterized. OBJECTIVES: To evaluate the safety and efficacy of pooled cryopreserved equine umbilical cord blood-derived MSCs (eCB-MSCs) combined with hyaluronic acid (HA) for surgically induced fetlock OA in horses, using integrated clinical, imaging, and synovial biomarker outcomes. STUDY DESIGN: Prospective randomized experimental study. METHODS: Twelve Standardbred horses underwent arthroscopic creation of an osteochondral (OC) fragment on the proximal phalanx (P1) in one metacarpophalangeal joint and were randomized to receive intra-articular eCB-MSC + HA or saline 6 weeks after surgery. At 12 weeks, a second surgery enabled joint sampling and arthroscopic scoring. Clinical lameness was assessed using subjective scoring and inertial sensor-based gait analysis. Structural progression was evaluated using radiography and high-field MRI with a modified Whole-Organ Magnetic Resonance Imaging Score (WORMS). Synovial fluid cytokines and chemokines were quantified longitudinally. Treatment effects and interactions with time-of-treatment inflammatory status and fragment size were analyzed using mixed models and non-parametric methods. RESULTS: Both treatments were well tolerated with no clinically relevant adverse joint reactions. eCB-MSC + HA treated horses showed significantly greater improvement in both objective and subjective lameness scores than saline-treated controls. MRI showed stabilization or improvement of WORMS scores in eCB-MSC + HA treated joints, whereas saline-treated joints exhibited structural deterioration over time; radiographic and arthroscopic scores did not differ significantly between groups. Synovial cytokine responses were baseline- and fragment-dependent, with attenuation of pro-inflammatory mediators (including IL-1β and TNF-α) and preservation of regulatory immune signaling in eCB-MSC + HA treated joints. Pre-treatment WORMS scores were associated with multiple cytokines. CONCLUSION: eCB-MSC + HA therapy was safe and was associated with improved clinical signs, MRI-detected structural benefits, and immunomodulatory effects. Because the between group structural difference was significant on MRI but not on radiography or arthroscopy, and given the small sample size and short follow-up, these results suggest a symptom-modifying and potential disease-modifying role for eCB-MSC + HA in early OA, pending confirmation in larger, longer-term studies.