title: 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: BACKGROUND
  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.
authors.affiliation: Department of Clinical Studies, University of Guelph, Ontario, Canada.
authors.forename: L B
authors.initials: LB
authors.lastname: Williams
authors.affiliation: Department of Clinical Studies, University of Guelph, Ontario, Canada.
authors.forename: J B
authors.initials: JB
authors.lastname: Koenig
authors.affiliation: Department of Clinical Studies, University of Guelph, Ontario, Canada.
authors.forename: B
authors.initials: B
authors.lastname: Black
authors.affiliation: Department of Clinical Studies, University of Guelph, Ontario, Canada.
authors.forename: T W G
authors.initials: TW
authors.lastname: Gibson
authors.affiliation: Department of Pathobiology, University of Guelph, Ontario, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Sharif
authors.affiliation: Department of Biomedical Sciences, University of Guelph, Ontario, Canada.|Department of Clinical Studies, Orthopaedic Research Lab, Aarhus University, Denmark.
authors.forename: T G
authors.initials: TG
authors.lastname: Koch
mesh_terms: D000818:Animals; D005260:Female; D005312:Fetal Blood / Q000166:cytology*; D006734:Horse Diseases / Q000209:etiology / Q000628:therapy; D006736:Horses; D007249:Inflammation / Q000139:chemically induced / Q000209:etiology / Q000662:veterinary*; D007592:Joint Diseases / Q000209:etiology / Q000628:therapy / Q000662:veterinary; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D013582:Synovial Fluid / Q000166:cytology*; D013585:Synovitis / Q000139:chemically induced / Q000662:veterinary*
chemical_list: D008070:Lipopolysaccharides
keywords: cord blood; horse; joint; stem cell; synovitis