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Autologous stem cell therapy in knee osteoarthritis: a systematic review of randomised controlled trials
  1. Tom GH Wiggers1,
  2. Marinus Winters2,
  3. Noortje AC Van den Boom3,
  4. Hidde J Haisma4,
  5. Maarten H Moen5
  1. 1Sports Medicine, St Anna Hospital, Geldrop, The Netherlands
  2. 2Research Unit for General Practice in Aalborg, Department of Clinical Medicine, Aalborg Universitet Det Sundhedsvidenskabelige Fakultet, Aalborg, Denmark
  3. 3Department of Medicine, Maastricht University, Maastricht, The Netherlands
  4. 4Department of Pharmaceutical Gene Modulation, Rijksuniversiteit Groningen, Groningen, Groningen, The Netherlands
  5. 5Medical Staff, NOC NSF, Arnhem, Gelderland, The Netherlands
  1. Correspondence to Mr Tom GH Wiggers, Sports Medicine, St Anna Hospital, Geldrop, The Netherlands; t.wiggers{at}


Objective Stem cell therapy is increasingly used for knee osteoarthritis (KOA). We aimed to review the evidence of autologous mesenchymal stem cell therapy on pain, function and severity on imaging in KOA.

Design Systematic review of randomised controlled trials (RCTs).

Eligibility criteria RCTs evaluating autologous mesenchymal stem cell (MSC) therapy on patient-reported outcome measures and disease severity.

Data sources Seven databases were searched until 31 December 2020.

Risk of bias and data synthesis Risk of bias was assessed using the ROB V.2. We used Grading of Recommendations Assessment, Development and Evaluation to appraise the certainty of the evidence. Data were synthesised descriptively.

Results Fourteen RCTs were included. A total of 408 patients with KOA received MSC therapy derived from bone marrow, adipose tissue or activated peripheral blood. After 1 year, 19 of 26 (73%) clinical outcome measures improved with MSCs compared with control. In the MSC group, patients improved by 1.8–4.4 points on the Visual Analogue Scale (0–10) and 18–32 points of the Knee Osteoarthritis Outcome Score (0–100). Four studies showed better disease severity on imaging after MSC compared with control at 1 year. Ten of 14 (71%) RCTs were at high risk of bias on all outcomes. No serious adverse events were reported after MSC therapy during a maximum of 4 years follow-up.

Conclusion We found a positive effect of autologous MSC therapy compared with control treatments on patient-reported outcome measures, and disease severity. The certainty of this evidence was low to very low.

PROSPERO registration number CRD42019120506

  • knee
  • osteoarthritis
  • treatment
  • review
  • cartilage

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  • Twitter @wiggersrunning, @marinuswinters

  • Collaborators not applicable.

  • Contributors TW contributed to the study conception and design, data collection, and drafting and revision of the manuscript. MW contributed to the study conception and design and drafting and revision of the manuscript. NACB contributed to the data analysis and drafting and revision of the manuscript. HH contributed to drafting and revision of the manuscript. MM contributed to study conception and design, the data analysis and drafting and revision of the manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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