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New Autologous MSC Trial in Osteoarthritic Patients Suggests Safety and Hints at Efficacy

Review of “Bone Marrow Mesenchymal Stromal Cells in Patients with Osteoarthritis Results in Overall Improvement in Pain and Symptoms and Reduces Synovial Inflammation” from STEM CELLS Translational Medicine by Stuart P. Atkinson

The treatment of osteoarthritis (OA) with mesenchymal stem cell (MSC) therapy has met some success in small-phase trials [1-4], with some reports of improvements to cartilage morphology [5-7]. However, there remains a knowledge gap with regards to the MSC dosing and selection criteria and the therapeutic mechanisms at play; do MSCs resolve inflammation, or do they display chondroprotective/regenerative effects?

In an attempt to address these critical questions, researchers from the laboratory of Sowmya Viswanathan (University Health Network, Toronto, Ontario, Canada) initiated a clinical trial of autologous bone marrow-derived MSC therapy in twelve patients with moderate to severe knee osteoarthritis. However, this new STEM CELLS Translational Medicine article also reports on patient‐reported outcomes, imaging, biomarkers, and molecular fingerprinting to obtain a better understanding of MSC dosing, mechanisms of action, and donor selection [8].

Here are the main points from this new study by Chahal et al.:

  • Osteoarthritis patients received a single intra‐articular injection of 1, 10, or 50 million MSCs
  • The trial reported minor, transient adverse events in four patients, but no serious adverse events in the 12-month follow up
  • MSC treatment prompted significant overall improvements in pain, symptom, quality of life, and stiffness scores
    • Patients receiving the largest dose reported improvements in most patient-reported outcome measures
    • Furthermore, these patients exhibited lower cartilage catabolic biomarkers, suggesting a chondroprotective effect of MSCs
  • Of note, hyaline cartilage morphology and collagen content score failed to improve in any patient
  • Analysis of synovial fluid revealed a decrease in pro‐inflammatory monocytes/macrophages and interleukin 12 levels after MSC injection
    • High dose MSC treatment led to reduced levels of synovitis
    • Interestingly, anti‐inflammatory marker expression in MSCs correlated to patient-reported outcome measures over 12 months, suggesting use as a functional biomarker
    • Overall, this suggests that MSCs act by reducing synovial inflammation in osteoarthritis

In summary, this new trial indicates the safety of autologous bone marrow MSCs for the treatment of knee osteoarthritis, while also providing hints of efficacy through chondroprotective effects and the dampening of inflammatory responses and identifying potential selection markers for therapeutically relevant MSCs. The authors now hope to fully confirm these findings in larger, controlled, randomized trials to measure multimodal outcomes in MSC treatment of osteoarthritis.

For more on MSC therapy for knee osteoarthritis, stay tuned to the Stem Cells Portal!

References

  1. Vega A, Martín-Ferrero MA, Del Canto F, et al., Treatment of Knee Osteoarthritis With Allogeneic Bone Marrow Mesenchymal Stem Cells: A Randomized Controlled Trial. Transplantation 2015;99:1681-1690.
  2. Orozco L, Munar A, Soler R, et al., Treatment of Knee Osteoarthritis With Autologous Mesenchymal Stem Cells: A Pilot Study. Transplantation 2013;95.
  3. Gupta PK, Chullikana A, Rengasamy M, et al., Efficacy and safety of adult human bone marrow-derived, cultured, pooled, allogeneic mesenchymal stromal cells (Stempeucel®): preclinical and clinical trial in osteoarthritis of the knee joint. Arthritis Research & Therapy 2016;18:301
  4. Yubo M, Yanyan L, Li L, et al., Clinical efficacy and safety of mesenchymal stem cell transplantation for osteoarthritis treatment: A meta-analysis. PLOS ONE 2017;12:e0175449.
  5. Jo CH, Lee YG, Shin WH, et al., Intra-Articular Injection of Mesenchymal Stem Cells for the Treatment of Osteoarthritis of the Knee: A Proof-of-Concept Clinical Trial. STEM CELLS 2014;32:1254-1266.
  6. de Windt TS, Vonk LA, Slaper-Cortenbach ICM, et al., Allogeneic Mesenchymal Stem Cells Stimulate Cartilage Regeneration and Are Safe for Single-Stage Cartilage Repair in Humans upon Mixture with Recycled Autologous Chondrons. STEM CELLS 2017;35:256-264.
  7. Murphy JM, Fink DJ, Hunziker EB, et al., Stem cell therapy in a caprine model of osteoarthritis. Arthritis & Rheumatism 2003;48:3464-3474.
  8. Chahal J, Gómez-Aristizábal A, Shestopaloff K, et al., Bone Marrow Mesenchymal Stromal Cell Treatment in Patients with Osteoarthritis Results in Overall Improvement in Pain and Symptoms and Reduces Synovial Inflammation. STEM CELLS Translational Medicine 2019;8:746-757.