Systematic review and meta-analysis of adult multipotent stromal/stem cell treatment for equine tendinopathy and desmopathy.

Overview

• This study systematically reviewed and analyzed existing research on the effectiveness of adult multipotent stromal/stem cell (MSC) treatments for tendon and ligament injuries (tendinopathy and desmopathy) in horses.
• The findings suggest that MSC therapy improves clinical outcomes such as return to soundness, lameness scores, and tissue microstructure, although effects on molecular and mechanical tissue properties remain unclear.

Research Purpose and Background

• Equine tendinopathy and desmopathy are common injuries affecting tendons and ligaments in horses, which can impair performance and cause lameness.
• In recent decades, cell-based therapies, particularly those using adult multipotent stromal/stem cells (MSCs), have emerged as promising treatment options aimed at improving healing and recovery.
• The study aimed to critically evaluate the overall effectiveness of MSC treatments for these injuries by systematically reviewing and synthesizing data from existing studies.

Methodology

• Database Search: The researchers performed a literature search in PubMed and Web of Science covering studies from January 2001 to June 2025.
• Search Terms: Included combinations of keywords related to horses, tendon and ligament injuries, stem/stromal cells, and cell therapy.
• Inclusion Criteria: Studies involving equine tendinopathy or desmopathy treatments with adult MSCs were selected following PRISMA guidelines, ensuring rigor in systematic review process.
• Data Extraction: Independent reviewers collected detailed information including:
  • Horse demographics (signalment), lesion location and cause (etiology)
  • Treatment details
  • Clinical outcomes such as return to soundness (healed and pain-free state) or performance levels
  • Quantitative measures like lameness scores and ultrasound tissue characterization
  • Biological assessments including gene expression, tissue composition, mechanical properties, and microstructure
• Risk of Bias Assessment: To evaluate the reliability of included studies’ results.
• Data Synthesis & Meta-Analysis: Used fixed- or random-effects statistical models:
  • Effect sizes calculated as mean standardized differences or odds ratios with 95% confidence intervals
  • Random-effects models applied when study heterogeneity was significant to better accommodate variability

Results

• Seventeen studies met all inclusion criteria and were analyzed in detail.
• Clinical outcomes:
  • MSC therapy was associated with improved return to soundness and performance, indicating better recovery and functional improvement.
  • Reduction in lameness scores suggested decreased pain and improved limb function following MSC treatment.
  • Ultrasound assessment showed favorable changes in tissue structure with MSC therapy, supporting enhanced healing quality.
  • Tissue microstructure analysis also indicated improvements when MSCs were used, promoting better tendon and ligament organization.
• Molecular and tissue-level parameters:
  • No statistically significant differences were found between MSC treatment and control groups in terms of tissue gene expression, composition (e.g., extracellular matrix components), or mechanical properties.
  • This suggests that while clinical signs improve, underlying molecular and biomechanical recovery may require further study or longer follow-up.

Conclusions and Recommendations

• The review supports that adult MSC therapy positively affects clinical recovery in horses with tendon and ligament injuries.
• Despite improvements in clinical outcomes and tissue microstructure, there is insufficient evidence to confirm benefits at the molecular and mechanical tissue levels.
• Future research should focus on:
  • Randomized controlled trials (to minimize bias and establish causation)
  • Standardization of cell isolation, preparation techniques, and dosages to ensure consistency and comparability across studies
  • Use of standardized and comprehensive outcome measures including mechanical properties and molecular markers
  • Long-term follow-up to assess the durability of the recovery at all tissue levels