Current Evidence of Mesenchymal Stem Cells Use in the Treatment of Tendon Disorders: A Systematic Review, Meta-analysis, and Meta-regression of Prospective Clinical Studies

Abstract

Purpose Although several studies with animals have reported the effects of mesenchymal stem cells (MSCs) for tendon regeneration, little is known about the efficacy and safety of MSCs in human tendon disorders. We performed this meta-analysis to evaluate the efficacy and safety of MSC therapy in patients with tendon disorders enrolled in prospective clinical studies. Methods We systematically searched prospective clinical studies investigating the effects of MSCs administration on human tendon disorders with at least a 6-month follow-up period on PubMed-Medline, Embase, and Cochrane Library databases. The primary outcome of interest was the change in pain on motion related to tendon disorders. We performed a pairwise meta-analysis using the fixed-effects model to assess treatment response, which was calculated by the standardized mean difference. Meta-regression analyses were performed to assess the relationship between MSCs dose and pooled effect sizes in each cell dose. Results Four prospective clinical trials investigating the effect of MSCs on tendon disorders were retrieved. MSCs showed significant pooled effect size (overall Hedge’s g pooled standardized mean difference (SMD) = 1.868; 95% confidence interval [CI], 1.274–2.462; P < 0.001). The treatment with MSCs improved all the aspects analyzed, i.e. pain, functional scores, radiologic parameters (magnetic resonance image or ultrasonography), and arthroscopic findings. In the meta-regression analysis, there was a significant cell dose-dependent response in pain relief (Q = 9.06, P = 0.029). While three studies reported mild adverse events after MSCs injection, these were not severe and relieved spontaneously. Conclusions Our meta-analysis revealed that MSC therapy may improve pain, function, radiologic, and arthroscopic parameters in patients with tendon disorders. Due to the small number of studies in this meta-analysis and considering the increasing MSCs applications, there is a strong need for large-scale randomized controlled trials to confirm the long-term functional improvement as well as the adverse effects of MSC therapies in tendon disorders.