Research on Umbilical Cord Blood Mesenchymal Stromal Cells within the Synovitis Model

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A new article has been published that is titled, “Equine allogeneic umbilical-cord-blood mesenchymal stromal cells reduce synovial fluid nucleated cell count and induce mild self-limiting inflammation when evaluated in a LPS induced synovitis model.” This article is available for purchase on Wiley.com.

SUMMARY

Reasons for Performing Study

Improvement has been reported following intra-articular (IA) injection of mesenchymal stromal cells (MSC) in several species. These observations have led to use of IA MSC in equine practice with little understanding of the mechanisms by which perceived improvement occurs.

Objectives

To evaluate the effect of IA allogeneic umbilical-cord-blood- (CB-) derived MSC using lipopolysaccharide (LPS) induced synovitis model. We hypothesised IA CB-MSC would decrease inflammatory response associated with LPS injection.

Study Design

Randomised, blinded experimental study.

Methods

Feasibility studies evaluated IA LPS or CB-MSC alone into the tarsocrural joint. Principal study middle carpal joint LPS synovitis was induced bilaterally then CB-MSC were injected into one middle carpal joint. Lameness, routine synovial fluid (SF) analysis, and SF 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-MSC resulted in mild synovitis that resolved without treatment. Mild (grade 1-2) lameness in the CB-MSC-treated limb was observed in 2 horses, severe lameness (grade 4) in the third 24h post-injection. Lameness did not correlate with synovitis induced by CB-MSC injection.

Simultaneous injection of LPS and CB-MSC resulted in significant reduction in SF total nucleated, neutrophil, and mononuclear cell numbers compared to contralateral LPS-only joints. No difference was detected in other parameters associated with SF analysis or in SF biomarkers. The incidence of lameness was only different from baseline at 8 h, where horses were lame in CB-MSC limbs.

Conclusions

Allogeneic CB-MSC reduced SF cell populations and stimulated mild self-limiting inflammation in the synovitis model. Continued evaluation of the effects of IA CB-MSC therapy on synovitis in horses is needed to evaluate anti- and pro-inflammatory properties of CB-MSC. Immediate interests are dose, timing of treatment, and treatment frequency.

Authors

L.B. Williarms, J. B. Koenig, B. Black, and T.W.G. Gibson, Departments of Clinical Studies, University of Guelph, Guelph, Ontario, Canada; S. Sharif, Pathobiology, University of Guelph, Guelph, Ontario, Canada; T.G. Koch, Biomedical sciences, University of Guelph, Guelph, Ontario, Canada, and Department of Clinical Studies, Orthopaedic Research Lab, Aarhus University, Aarhus, Denmark.