Toll-like receptor 3-activated allogeneic umbilical cord blood-derived mesenchymal stromal cells as an adjunct for the treatment of synovial sepsis in 3 horses.

Research Summary

• This study describes the use of Toll-like receptor 3 (TLR-3)-activated allogeneic umbilical cord blood-derived mesenchymal stromal cells (CB-MSCs) to treat synovial sepsis in three horses.
• The treatment was used as an adjunct alongside conventional therapies for cases involving chronic or antimicrobial-resistant (AMR) septic synovitis, showing positive outcomes.

Background and Objective

• Synovial sepsis is a serious joint infection that can cause severe lameness and swelling in horses, often challenging to treat especially when antimicrobial resistance is present.
• The study aimed to explore the practicality and effectiveness of TLR-3-activated CB-MSCs as an additional treatment option for such infections, particularly in cases resistant to standard antimicrobials.

Case Presentations

• Three horses were featured in the study, each presenting with septic synovitis characterized by clinical signs such as:
  • Grade 4/5 lameness (severe limping)
  • Joint effusion (fluid accumulation)
  • Limb heat and swelling
  • Synovial fluid consistent with infection
• Timing and background of infections:
  • Case 1: Presented 3 weeks after clinical sign onset.
  • Case 2: Developed infection 4 weeks after elective arthroscopy.
  • Case 3: Developed infection 5 weeks after third phalanx fracture fixation.
• Microbiology:
  • Cases 2 and 3 had antimicrobial-resistant bacteria identified via culture and sensitivity tests.
• Additional findings through imaging:
  • Septic synovitis confirmed ultrasonographically and radiographically in all cases.
  • Osteitis (bone inflammation) in two cases.
  • Presumptive septic tendinitis in one case.

Treatment Protocol

• All horses received standard treatment including:
  • Systemic antibiotics.
  • Regional (localized) antimicrobial administration.
  • Synovial lavage (joint flushing).
• Use of TLR-3-activated CB-MSCs:
  • In two cases, these cells were introduced after conventional treatments failed to resolve the infection.
  • In the third case, the cells were used early due to infection chronicity and the presence of septic tendinitis.
  • Twenty million TLR-3-activated CB-MSCs were administered either by regional limb perfusion or direct intra-articular injection based on the clinical scenario.

Outcomes

• All three horses showed resolution of septic synovitis following the combined treatments including the CB-MSCs adjunct therapy.
• The results indicate the potential for TLR-3-activated CB-MSCs to enhance recovery, especially in challenging or resistant infections.

Significance and Implications

• Antimicrobial resistance poses a growing challenge in veterinary and human medicine, necessitating new therapeutic approaches.
• This study highlights the promising role of activated mesenchymal stromal cells derived from umbilical cord blood as adjunctive treatment, potentially enhancing antimicrobial effectiveness and supporting tissue healing.
• The immune-modulating properties of TLR-3 activation may improve the therapeutic impact of CB-MSCs by boosting their antimicrobial and anti-inflammatory effects.
• Although this is a small case series, it provides a foundation for future, larger studies to validate safety and efficacy.