Intra-Articular Injection of 2 Different Dosages of Autologous and Allogeneic Bone Marrow- and Umbilical Cord-Derived Mesenchymal Stem Cells Triggers a Variable Inflammatory Response of the Fetlock Joint on 12 Sound Experimental Horses

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English. Osteoarthritis is a significant and costly cause of pain for both humans and horses. The horse has been identified as a suitable modelfor human osteoarthritis. Regenerative therapy with allogeneic mesenchymal stem cells (MSCs) is a promising treatment, but thesafety of this procedure continues to be debated. The aim of this study is to evaluate the safety of intra-articular injections ofallogeneic MSCs on healthy joints by comparing two different dosages and two different tissue sources, namely, bone marrowand umbilical cord blood, with a placebo treatment on the same individuals. We also assessed the influence of autologous versusallogeneic cells for bone marrow-derived MSC treatment. Twelve clinically sound horses were subjected to injections in their 4fetlock joints. Each of the three fetlocks was administered a different MSC type, and the remaining fetlock was injected withphosphate-buffered saline as a control. Six horses received 10 million cells per joint, and the 6 other horses received 20 millioncells per joint. Clinical and ultrasound monitoring revealed that allogeneic bone marrow-derived MSCs induced significantlymore synovial effusion compared to umbilical cord blood-derived MSCs but no significant difference was noted within thesynovial fluid parameters. The administration of 10 million cells in horses triggered significantly more inflammatory signs thanthe administration of 20 million cells. Mesenchymal stem cell injections induced mild to moderate local inflammatory signscompared to the placebo, with individual variability in the sensitivity to the same line of MSCs. Understanding the behavior ofstem cells when injected alone is a step towards the safer use of new strategies in stem cell therapy, where the use of either MSCsecretome or MSCs combined with biomaterials could enhance their viability and metabolic activity