Efficacy and Safety of Intra-Articular Cell-Based Therapy for Osteoarthritis: Systematic Review and Network Meta-Analysis.

OBJECTIVE Osteoarthritis (OA) is a chronic joint disease characterized by degeneration of articular cartilage and secondary osteogenesis. Cell-based agents, such as mesenchymal stem cells, have turned into the most extensively explored new therapeutic agents for OA. However, evidence-based research is still lacking. METHODS We searched public databases up to February 2020 and only included randomized controlled trials. The outcomes included the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), the Knee Injury and Osteoarthritis Outcome Score (KOOS), the visual analogue scale (VAS) score, and serious adverse events (SAEs). A network meta-analysis was also performed in this work. RESULTS We included 13 studies in the meta-analysis. The effect size showed that cell-based therapy did not significantly reduce the WOMAC score at the 6-month follow-up (standard mean difference [SMD] -3.6; 95% confidence interval [CI] -0.90 to 0.18; P = 0.1928). However, cell-based therapy significantly improved the KOOS at the 12-month follow-up (SMD 0.68; 95% CI 0.07-1.30; P = 0.0288) and relieved pain (SMD -1.05; 95% CI -1.46 to -0.64; P < 0.0001). The findings also indicated that high-dosage adipose-derived mesenchymal stem cells (ADMSCs) may be more advantageous in terms of long-term effects. CONCLUSIONS Cell-based therapy had a better effect on KOOS improvement and pain relief without safety concerns. However, cell-based therapy did not show a benefit in terms of the WOMAC. Allogeneic cells might have advantages compared to controls in the WOMAC and KOOS scores. The long-term effect of high-dose ADMSC treatment for OA is worthy of further study.