Efficacy and safety of intra-articular injection of mesenchymal stem cells in the treatment of knee osteoarthritis: A systematic review and meta-analysis

Wei Ma, Cuimiao Liu, Shilu Wang, Honghao Xu, Haichao Sun, Xiao Fan, Wei Ma, Cuimiao Liu, Shilu Wang, Honghao Xu, Haichao Sun, Xiao Fan

Abstract

Objective: To evaluate the effects and safety of intra-articular injection of mesenchymal stem cells on patients with knee osteoarthritis by a systematic review and meta-analysis.

Methods: PubMed, EMBASE, and Cochrane Library were retrieved. An assessment of the risk of bias was done through the Cochrane Collaborative Bias Risk Tool, publication bias was assessed by plotting funnel plots and Egger tests. Pain and functional improvements in patients with knee osteoarthritis were determined by changes in VAS scores and WOMAC scores at baseline and follow-up endpoints. For the evaluation of MRI, the WORMS score and changes in cartilage volume were used. In addition, the number of adverse events in the intervention group and the control group were counted to explore the safety.

Results: A total of 10 randomized controlled trials involving 335 patients were included. In the pooled analysis, compared with the control groups, the VAS scores of MSC groups decreased significantly (MD,-19.24; 95% CI: -26.31 to -12.18, P < .00001. All of the WOMAC scores also improved significantly: the total scores (SMD, - 0.66; 95% CI: - 1.09 to -0.23, P = .003), pain scores (SMD, - 0.46; 95% CI: - 0.75 to -0.17, P = .002), stiffness scores (SMD, -0.32; 95% CI: -0.64 to 0.00 P = 0.05), and functional scores (SMD, -0.36; 95% CI: -0.69 to -0.04, P = .03). Two studies with non-double-blind designs were the main source of heterogeneity. In terms of cartilage repair, there was no significant difference in the WORMS score, but there was a significant increase in cartilage volume in the MSC group (SMD, 0.69; 95% CI: 0.25 to 1.13, P = .002). The proportion of patients with adverse events in the MSCs treatment group was significantly higher than that in the control group (OR, 3.20; 95% CI: 1.50 to 6.83, P = .003).

Conclusions: Intra-articular injection of mesenchymal stem cells is effective and safety to relieve pain and improve motor function of patients with knee osteoarthritis in a short term which is different to conclusions of previous study.

Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Figure 1
Figure 1
The process of literature screening in strict accordance with the inclusion/exclusion criteria. RCT, randomized controlled trial.
Figure 2
Figure 2
Summary of the risk of bias assessment for the included studies.
Figure 3
Figure 3
Evaluation of publication bias by funnel plot symmetry (A) Funnel plot of VAS scores (Egger, P = .49), (B) Funnel plot of WOMAC total scores (Egger, P = .22).
Figure 4
Figure 4
Forest plots of mean difference with 95% CI in visual analog scale (VAS) scores. Fixed-effects models were used.
Figure 5
Figure 5
Forest plots of standardized mean difference with 95% CI in WOMAC scores. (A) WOMAC total scores. (B) WOMAC pain scores. (C) WOMAC stiffness scores. (D) WOMAC functional scores. Random effects models were used in A, Fixed-effect models were used in B, C, and D.
Figure 6
Figure 6
Forest plots of mean difference with 95% CI in WORMS scores. Fixed-effects models were used.
Figure 7
Figure 7
Forest plots of standardized mean difference with 95% CI in changes in cartilage volume. Fixed-effect effects models were used.
Figure 8
Figure 8
Forest plots of odds ratios with 95% CI in number of patients with adverse events. Fixed-effects models were used.

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