Mesenchymal Stem Cells Injection Is More Effective Than Hyaluronic Acid Injection in the Treatment of Knee Osteoarthritis With Similar Safety: A Systematic Review and Meta-analysis

Purpose: To evaluate the efficacy and safety of intra-articular injection of mesenchymal stem cells (MSCs) versus hyaluronic acid (HA) in the treatment of knee osteoarthritis (KOA). Methods: Eligible randomized controlled trials (RCTs) were identified through a search of PubMed, Embase, the Cochrane Library, Web of Science, SinoMed, and CNKI databases from inception to March 2024. For meta-analysis, data on clinical outcomes were measured using visual analog scale (VAS) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and data on cartilage repair were measured using the Whole-Organ Magnetic Resonance Imaging Score (WORMS); data on safety were evaluated by the incidence of adverse events. Two researchers independently read the included literature, extracted data and evaluated the quality, used the Cochrane risk bias assessment tool for bias risk assessment, and used RevMan5.3 software for meta-analysis. Results: Ten RCTs involving 818 patients with KOA ranging from Ito III on the KellgrenLawrence grading scale were included in this meta-analysis. Meta-analysis results showed that at 12 months, the WOMAC total score (mean difference [MD] = -10.22, 95% confidence interval [CI]: -14.86 to -5.59, P < .0001, Z = 4.32), VAS score (MD = -1.31, 95% CI: -1.90 to -0.73, P < .0001, Z = 4.40); and WORMS score (MD = -26.01, 95% CI: -31.88 to -20.14, P < .001, Z = 8.69) of the MSCs group all decreased significantly (P < .05) compared with the HA control group and reached the minimal clinically important differences. Furthermore, there was no significant difference in the incidence of adverse events (relative risk = 1.54, 95% CI: 0.85-2.79, P = .16, I-2 = 0) between the 2 groups (P> .05). Conclusions: In terms of efficacy, the clinical effects of intra-articular injection therapy using MSCs for KOA are superior to those of HA, and the cartilage repair effect of MSCs is also markedly better than that of HA. Although the clinical effects varied across time periods, the functional score reached the minimum clinically significant difference at both 6 and 12 months. In terms of safety, adverse reactions mainly manifest as joint pain, swelling, and joint effusion. Both intra-articular injections of MSCs and HA did not result in severe adverse reactions, indicating that MSCs and HA have similar safety profiles. Level of Evidence: Level I, meta-analysis of Level I studies.