Ann Rehabil Med.  2021 Aug;45(4):274-283. 10.5535/arm.21078.

Mesenchymal Stem Cells Use in the Treatment of Tendon Disorders: A Systematic Review and Meta-Analysis of Prospective Clinical Studies

• Cho WS
• Chung SG
• Kim W
• Jo CH
• Lee SU
• Lee SY

• KMID: 2519634
• DOI: http://doi.org/10.5535/arm.21078

Abstract

Objective
To evaluate the efficacy and safety of mesenchymal stem cells (MSCs) therapy in patients with tendon disorders enrolled in prospective clinical studies.
Methods
We systematically searched prospective clinical studies that investigated the effects of MSC administration on human tendon disorders with at least a 6-month follow-up period in the PubMed-MEDLINE, EMBASE, and Cochrane Library databases. The primary outcome of interest was the change in pain on motion related to tendon disorders. Meta-regression analyses were performed to assess the relationship between MSC dose and pooled effect sizes in each cell dose.
Results
Four prospective clinical trials that investigated the effect of MSCs on tendon disorders were retrieved. MSCs showed a significant pooled effect size (overall Hedges’ g pooled standardized mean difference=1.868; 95% confidence interval, 1.274–2.462; p<0.001). The treatment with MSCs improved all the aspects analyzed, namely pain, functional scores, radiological parameters (magnetic resonance image or ultrasonography), and arthroscopic findings. In the meta-regression analysis, a significant cell dose-dependent response in pain relief (Q=9.06, p=0.029) was observed.
Conclusion
Our meta-analysis revealed that MSC therapy may improve pain, function, radiological, and arthroscopic parameters in patients with tendon disorders. A strong need for large-scale randomized controlled trials has emerged to confirm the long-term functional improvement and adverse effects of MSC therapies in tendon disorders.

Keyword

Mesenchymal stem cells, Tendinopathy, Rotator cuff, Tennis elbow, Meta-analysis

Figure

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  Fig. 1. The Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISRMA) flow diagram detailing the selection process of relevant clinical studies.

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  Fig. 2. Forest plot of the pooled effect of mesenchymal stem cells (MSCs) on tendon disorders determined by a fixed-effects meta-analysis. Effect sizes are indicated as Hedges’ g standardized mean differences and 95% confidence intervals.

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  Fig. 3. Forest plots of the effects of trial/cell dose-level characteristics of mesenchymal stem cells (MSCs) analyzed as outcome variables: (A) pain (primary outcome), (B) functional scores, (C) radiological parameters, and (D) arthroscopic findings.

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  Fig. 4. Meta-regression of the standardized mean differences in means for cell doses. The area of the circles is proportional to the weights of the studies in the regression.

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