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Simple Summary: Synovitis frequently affects joints in horses and can result in lameness. Synovitis results in joint capsule distention and inflammation of the joint environment, which can lead to more serious complications, such as osteoarthritis, if not addressed early. Researchers are searching for a treatment to interrupt this progression and address the synovitis prior to osteoarthritis developing. We present a study that assesses the safety and efficacy of a single administration of 10 million cryopreserved allogeneic mesenchymal stromal cells (MSC) that were either activated (aMSC) or non-activated (naMSC) for the treatment of synovitis. The front or hind fetlock or a single joint of the carpus in 24 client-owned horses were split into two groups. Both MSC treatments resulted in positive clinical outcomes. When evaluating from Day 0 to Day 42, naMSC-treated horses improved by 0.79 lameness grades and aMSC-treated horses improved by 1.25 lameness grades. There was no significant difference between the two treatments for any outcome parameter. Owners were contacted at 12 and 18 weeks after treatment. All fifteen owners who returned questionnaires at 12 weeks were satisfied with their horses' response to treatment. Eighteen of the twenty-three questionnaires that were returned at Week 18 indicated that the owners were satisfied with their horses' response to treatment. Synovitis is present before and during osteoarthritis in horses and can result in performance-limiting lameness. Twenty-four horses with lameness localized to the metacarpo-/metatarsophalangeal joint or a single joint of the carpus were enrolled in this study. We evaluated the response of intra-articular injection with 10 million activated (aMSC) or non-activated (naMSC) allogeneic equine umbilical cord blood-derived mesenchymal stromal cells (MSCs). Subjective and objective lameness was assessed on Days 0, 1, 21, and 42. The treatment injection was randomly assigned and performed following the baseline assessment on Day 0. naMSC-treated horses had straight-line lameness scores that were significantly lower on Day 21 (1.0 ± 1.15) and Day 42 (1.13 ± 1.00) than on Day 0 (p = 0.0098 and p = 0.0418, respectively). aMSC-treated horses had straight-line lameness scores that were significantly lower on Day 21 (0.96 ± 1.03) and Day 42 (0.79 ± 1.05) than on Day 0 (p = 0.0011 and p < 0.0001, respectively). There was no significant difference between the treatment groups for any parameter at any timepoint. In conclusion, both aMSC and naMSC allogeneic MSCs resulted in significantly improved subjective lameness scores in horses when compared to baseline lameness scores. [ABSTRACT FROM AUTHOR]

Cationic contrast‐enhanced computed tomography (CECT) capitalizes on increased contrast agent affinity to the charged proteoglycans in articular cartilage matrix to provide quantitative assessment of proteoglycan content with enhanced images. While high resolution microCT has demonstrated success, we investigate cationic CECT use in longitudinal in vivo imaging at clinical resolution. We hypothesize that repeated administration of CA4+ will have no adverse side effects or complications, and that sequential in vivo imaging assessments will distinguish articular cartilage repair tissue from early degenerative and healthy cartilage in critically sized chondral defects. In an established equine translational preclinical model, lameness and synovial effusion scores are similar to controls after repeated injections of CA4+ (eight injections over 16 weeks) compared to controls. Synovial fluid total protein, leukocyte concentration, and sGAG and PGE2 concentrations and articular cartilage and synovial membrane scores are also equivalent to controls. Longitudinal in vivo cationic CECT attenuation in repair tissue is significantly lower than peripheral to (adjacent) and distantly from defects (remote sites) by 4 weeks (p < 0.001), and this difference persists until 16 weeks. At the 6‐ and 8‐week time points, the adjacent locations exhibit significantly lower cationic CECT attenuation compared with the remote sites, reflecting peri‐defect degeneration (p < 0.01). Cationic CECT attenuation at clinical resolution significantly correlates with cationic CECT (microCT) (r = 0.69, p < 0.0001), sGAG (r = 0.48, p < 0.0001), and ICRS II histology score (r = 0.63, p < 0.0001). In vivo cationic CECT imaging at clinical resolution distinguishes fibrous repair tissue from degenerative and healthy hyaline cartilage and correlates with molecular tissue properties of articular cartilage. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a common joint disease affecting humans and horses, resulting in significant morbidity, financial expense, and loss of athletic use. While the pathogenesis is incompletely understood, inflammation is considered crucial in the development and progression of the disease. Mesenchymal stromal cells (MSCs) have received increasing scientific attention for their anti-inflammatory, immunomodulatory, and pro-regenerative effects. However, there are concerns about their ability to become a commercially available therapeutic. Extracellular vesicles (EVs) are now recognized to play a crucial role in the therapeutic efficacy observed with MSCs and offer a potentially novel cell-free therapeutic that may negate many of the concerns with MSCs. There is evidence that EVs have profound anti-inflammatory, immunomodulatory, and pro-regenerative effects equal to or greater than the MSCs they are derived from in the treatment of OA. Most of these studies are in small animal models, limiting the translation of these results to humans. However, highly translational animal models are crucial for further understanding the efficacy of potential therapeutics and for close comparisons with humans. For this reason, the horse, which experiences the same gravitational impacts on joints similar to people, is a highly relevant large animal species for testing. The equine species has well-designed and validated OA models, and additionally, therapies can be further tested in naturally occurring OA to validate preclinical model testing. Therefore, the horse is a highly suitable model to increase our knowledge of the therapeutic potential of EVs., Competing Interests: Conflicts of interest All authors declared that there are no conflicts of interest.