Equine allogeneic umbilical cord blood derived mesenchymal stromal cells reduce synovial fluid nucleated cell count and induce mild self-limiting inflammation when evaluated in an lipopolysaccharide induced synovitis model.
Abstract: Improvement has been reported following intra-articular (i.a.) injection of mesenchymal stromal cells (MSCs) in several species. These observations have led to the use of i.a. MSCs in equine practice with little understanding of the mechanisms by which perceived improvement occurs. Objective: To evaluate the effect of i.a. allogeneic umbilical cord blood (CB-) derived MSCs using a lipopolysaccharide (LPS) induced synovitis model. We hypothesised that i.a. CB-MSCs would reduce the inflammatory response associated with LPS injection. Methods: Randomised, blinded experimental study. Methods: Feasibility studies evaluated i.a. LPS or CB-MSCs alone into the tarsocrural joint. In the principal study, middle carpal joint synovitis was induced bilaterally with LPS and then CB-MSCs were injected into one middle carpal joint. Lameness, routine synovial fluid analysis, and synovial fluid biomarkers were evaluated at 0, 8, 24, 48 and 72 h. Results: LPS injection alone resulted in transient lameness and signs of inflammation. In joints untreated with LPS, injection of 30 million CB-MSCs resulted in mild synovitis that resolved without treatment. Mild (grade 1-2) lameness in the CB-MSC-treated limb was observed in 2 horses and severe lameness (grade 4) in the 3rd, 24 h post injection. Lameness did not correlate with synovitis induced by CB-MSC injection. Simultaneous injection of LPS and CB-MSCs resulted in significant reduction in synovial fluid total nucleated, neutrophil and mononuclear cell numbers compared with contralateral LPS-only joints. No difference was detected in other parameters associated with synovial fluid analysis or in synovial fluid biomarkers. The incidence of lameness was only different from baseline at 8 h, where horses were lame in CB-MSC limbs. Conclusions: Allogeneic CB-MSCs reduced synovial fluid cell populations and stimulated mild self-limiting inflammation in the synovitis model. Continued evaluation of the effects of i.a. CB-MSC therapy on synovitis in horses is needed to evaluate anti- and proinflammatory properties of CB-MSCs. Immediate interests are dose, timing of treatment, and treatment frequency.
© 2015 EVJ Ltd.
Publication Date: 2015-08-14 PubMed ID: 26114736DOI: 10.1111/evj.12477Google Scholar: Lookup
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Summary
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The research explored the impact of allogenic umbilical cord blood-derived mesenchymal stromal cells (CB-MSCs) on synovitis, an inflammation of the synovial membrane, in horses. The findings suggest that these cells can significantly reduce the synovial fluid cell count associated with the disease, while inducing a mild, self-limiting inflammation in the affected horses.
Research Objective
- The study aimed to understand the metabolic effects of allogenic umbilical cord blood-derived mesenchymal stromal cells (CB-MSCs) on a model of lipopolysaccharide (LPS)-induced synovitis in horses.
- The study hypothesized that the introduction of CB-MSCs in the affected joint would reduce the inflammation associated with LPS injection.
Methodology
- This was a randomized, blinded experimental study.
- A simulated synovitis condition was created in horses using LPS injection into their tarsocrural joint and carpal joint.
- Subsequently, CB-MSCs were introduced into one of the middle carpal joints in the horses.
- Different parameters, such as lameness, routine synovial fluid analysis, and synovial fluid biomarkers, were evaluated at different time-intervals (0, 8, 24, 48, 72 hours).
Key Findings
- Introduction of LPS alone resulted in transient lameness and signs of inflammation. However, injection of CB-MSCs in isolation led to a self-limiting mild synovitis that didn’t require treatment.
- Certain horses showed lameness a day after the injection of CB-MSCs, but this didn’t correlate with the synovitis induced by CB-MSC injection.
- The simultaneous injection of LPS and CB-MSCs resulted in a significant reduction in synovial fluid total, neutrophil, and mononuclear cell counts compared to the joints that only received LPS.
- There were no significant differences in other parameters associated with the analysis of synovial fluid or synovial fluid biomarkers.
Conclusions
- The introduction of allogenic CB-MSCs was found to reduce synovial fluid cell populations and induce mild self-limiting inflammation in the model of synovitis in horses.
- The study recommends further investigation of the effects of CB-MSC therapy on synovitis in horses, given the potential of CB-MSCs to influence the pro- and anti-inflammatory properties.
- Aspects like dose, timing of treatment, and frequency of treatment will be pertinent in future studies on this front.
Cite This Article
APA
Williams LB, Koenig JB, Black B, Gibson TW, Sharif S, Koch TG.
(2015).
Equine allogeneic umbilical cord blood derived mesenchymal stromal cells reduce synovial fluid nucleated cell count and induce mild self-limiting inflammation when evaluated in an lipopolysaccharide induced synovitis model.
Equine Vet J, 48(5), 619-625.
https://doi.org/10.1111/evj.12477 Publication
Researcher Affiliations
- Department of Clinical Studies, University of Guelph, Ontario, Canada.
- Department of Clinical Studies, University of Guelph, Ontario, Canada.
- Department of Clinical Studies, University of Guelph, Ontario, Canada.
- Department of Clinical Studies, University of Guelph, Ontario, Canada.
- Department of Pathobiology, University of Guelph, Ontario, Canada.
- Department of Biomedical Sciences, University of Guelph, Ontario, Canada.
- Department of Clinical Studies, Orthopaedic Research Lab, Aarhus University, Denmark.
MeSH Terms
- Animals
- Female
- Fetal Blood / cytology
- Horse Diseases / etiology
- Horse Diseases / therapy
- Horses
- Inflammation / chemically induced
- Inflammation / etiology
- Inflammation / veterinary
- Joint Diseases / etiology
- Joint Diseases / therapy
- Joint Diseases / veterinary
- Lipopolysaccharides / toxicity
- Male
- Mesenchymal Stem Cell Transplantation
- Mesenchymal Stem Cells / physiology
- Synovial Fluid / cytology
- Synovitis / chemically induced
- Synovitis / veterinary
Citations
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