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

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). 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. Ten RCTs involving 818 patients with KOA ranging from I to Ⅲ on the Kellgren-Lawrence 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, I2 = 0) between the 2 groups (P > .05). Compared with HA, intra-articular injection of MSCs therapy appears to alleviate joint pain effectively, improving clinical function of KOA patients. These benefits are observed to last for at least 12 months without an increase in adverse events. Due to limited, varied, and lacking minimal clinically important differences results in existing literature, further research is needed. Level I, meta-analysis of Level I studies.