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