Evaluation of Allogeneic Bone-Marrow-Derived and Umbilical Cord Blood-Derived Mesenchymal Stem Cells to Prevent the Development of Osteoarthritis in An Equine Model

Abstract

Osteoarthritis (OA) is a significant cause of pain in both humans and horses with a high socio-economic impact. The horse is recognized as a pertinent model for human OA. In both species, regenerative therapy with allogeneic mesenchymal stem cells (MSCs) appears to be a promising treatment but, to date, no in vivo studies have attempted to compare the effects of different cell sources on the same individuals. The objective of this study is to evaluate the ability of a single blinded intra-articular injection of allogeneic bone-marrow (BM) derived MSCs and umbilical cord blood (UCB) derived MSC to limit the development of OA-associated pathological changes compared to placebo in a post-traumatic OA model applied to all four fetlock joints of eight horses. The effect of the tissue source (BM vs. UCB) is also assessed on the same individuals. Observations were carried out using clinical, radiographic, ultrasonographic, and magnetic resonance imaging methods as well as biochemical analysis of synovial fluid and postmortem microscopic and macroscopic evaluations of the joints until Week 12. A significant reduction in the progression of OA-associated changes measured with imaging techniques, especially radiography, was observed after injection of bone-marrow derived mesenchymal stem cells (BM-MSCs) compared to contralateral placebo injections. These results indicate that allogeneic BM-MSCs are a promising treatment for OA in horses and reinforce the importance of continuing research to validate these results and find innovative strategies that will optimize the therapeutic potential of these cells. However, they should be considered with caution given the low number of units per group.

Bone Marrow MSC Secretome Increases Equine Articular Chondrocyte Collagen Accumulation and Their Migratory Capacities

“…Indeed, beyond the chondrogenic differentiation potential of MSCs, their secretome could be a therapeutic alternative. MSC injection in the equine model led to a reduction in the progression of OA [ 11 ]. Nevertheless, concomitantly with allogeneic MSCs or even autologous injections, and despite their immunomodulatory properties, MSCs can stimulate innate immune responses which can result in deleterious inflammatory reactions [ 10 , 48 , 49 ].…”

“…Beyond their differentiation capacities, MSCs are able to secrete a large variety of soluble mediators and extracellular vesicles (EVs), known as the cell secretome, which participates in their most relevant physiological functions, including tissue repair and immunomodulation [ 5 , 6 ]. Indeed, several in vivo studies have shown that intra-articular injections of MSCs can promote the repair of chondral defects and/or reduce inflammation [ 7 , 8 , 9 , 10 , 11 ].…”

Temporal extracellular vesicle protein changes following intraarticular treatment with integrin α10β1-selected mesenchymal stem cells in equine osteoarthritis

“…The osteochondral fragment model used in this study has been shown to produce reliable post-traumatic OA in the middle carpal joint of horses ( 1 , 36 – 38 ). The mitigating effect of MSC treatment on the development of post-traumatic OA has been shown in a number of equine studies, although in different models, such as an osteochondral fragment model of the fetlock ( 39 , 40 ) a blunt impact model of the tarsus ( 15 ) and injection of the irritant amphotericin B ( 41 ). In these studies, the MSC-treated horses developed significantly less severe OA over time compared to the untreated control horses in terms of decreased synovial effusion and a higher SF viscosity and glycosaminoglycan content, decreasing lameness over time, less severe macroscopic cartilage erosions, less radiographic signs of OA, and less histologic cartilage fibrillation and subchondral sclerosis.…”

Highlights of recent clinically relevant papers

“…In this study Lélia Bertoni and co‐workers in France evaluated allogeneic bone‐marrow‐derived and umbilical cord blood‐ derived mesenchymal stem cells (MSCs) to prevent the development of osteoarthritis (OA) in an equine model .…”