The Effectiveness and Safety of Mesenchymal Stem Cells in the Treatment of Osteoarthritis: A Systematic Review and Meta-analysis of 28 Randomized Controlled Trials

Abstract

Objective. To evaluate the effectiveness and safety of mesenchymal stem cells (MSCs) in the treatment of osteoarthritis (OA). Methods. Chinese databases (such as CNKI and SinoMed) and English databases (such as PubMed and Embase) were searched to collect randomized controlled trials (RCTs) of MSCs in the treatment of OA. The retrieval time is from inception to October 10, 2021. The literature was strictly selected according to the inclusion and exclusion criteria, data was extracted, and the quality was evaluated. RevMan 5.3 software was used for meta-analysis. STATA was used to evaluate publication bias. The registration number of this systematic review and meta-analysis is CRD42021277145. Results. A total of 28 RCTs involving 1494 participants were included. The primary outcomes showed that MSCs may reduce WOMAC pain and VAS at the 3rd-month follow-up [WOMAC pain: -3.81 (-6.95, -0.68), P = 0.02 . VAS: -1.11 (-1.53, -0.68), P < 0.00001 ], and the effect lasts for at least 12 months [WOMAC pain: -4.29 (-7.12, -1.47), P = 0.003 . VAS: -1.77 (-2.43, -1.12), P < 0.00001 ]. MSCs may also reduce WOMAC stiffness and physical function at the 6th-month follow-up [WOMAC stiffness: -1.12 (-2.09, -0.14), P = 0.03 . WOMAC physical function: -4.40 (-6.84, -1.96), P = 0.0004 ], and the effect lasts for at least 12 months [WOMAC stiffness: -0.99 (-1.95, -0.03), P = 0.04 . WOMAC physical function: -3.26 (-5.91, -0.61), P = 0.02 ]. The improvement of WOMAC pain, VAS, WOMAC stiffness, and WOMAC physical function may be clinically significant. Meanwhile, after the MSC injection, Lequesne had been reduced compared with the control group [-4.49 (-8.21, -0.77), P = 0.002 ]. For adverse events, there is no significant difference in the safety of MSC injection and the control group [1.20 (0.97, 1.48), P = 0.09 ]. The quality of WOMAC physical function and adverse events were moderate. Conclusion. Based on current evidence, MSCs may be a safety therapy that have a good curative effect in the treatment of OA, the onset time is no later than 3 months, and the time to maintain the curative effect is no less than 12 months. However, these results should be generalized with caution due to the generally low quality of evidence and RCTs.

A systematic review, umbrella review, and quality assessment on clinical translation of stem cell therapy for knee osteoarthritis: Are we there yet?

“…Conversely, Long et al [ 105 ] showed that stem cells improved patients WOMAC scores better than conventional treatment (WMD = − 3.81; 95% CI [− 6.95, − 0.68]. At 6 months, only three studies [ 100 , 101 , 105 ] and at 12 months, only five [ 94 , 100 , 101 , 103 , 105 ] demonstrated that stem cells significantly improved patients WOMAC scores (Fig. 2 ).…”

“…At 3 months, the results from Qu et al [ 93 ] showed that stem cells were less effective than conventional treatment in improving the patients WOMAC scores (WMD = 3.35; 95% CI [0.01, 6.69]). Conversely, Long et al [ 105 ] showed that stem cells improved patients WOMAC scores better than conventional treatment (WMD = − 3.81; 95% CI [− 6.95, − 0.68]. At 6 months, only three studies [ 100 , 101 , 105 ] and at 12 months, only five [ 94 , 100 , 101 , 103 , 105 ] demonstrated that stem cells significantly improved patients WOMAC scores (Fig.…”

“…(2) VAS: Thirteen SRs/MAs reported VAS scores. At 3 months, Huang et al [ 97 ] and Long et al [ 105 ] found that stem cell transplantation significantly improved patients VAS scores compared to the opposite results obtained by Qu et al [ 93 ]. At 6 months, four studies concluded that stem cells did not improve the VAS scores of patients [ 92 , 103 , 104 , 106 ].…”

“…The studies in 11 of the 13 SRs/MAs were RCTs [ 92 – 102 ], while two included RCTs and Non-RCTs [ 103 , 104 ]. The analysis included patients ranging between 138 [ 100 ] and 1494 [ 102 ]. MSCs included in this analysis were ADMSCs, BMSCs, and UCMSCs.…”

“…High-quality studies supported by SRs/MAs are essential to inform clinical decisions. Our systematic summary of published SRs/MAs found that extending follow-up time from 3 to 24 months resulted in gradual improvement in pain scores for most patients, but WOMAC scores consistently yielded conflicting results across different SRs/MAs [ 93 , 105 ]. Possible reasons for this discrepancy include the limited sample sizes of the studies, the influence of individual studies on findings, and heterogeneity between different studies [ 94 ].…”