Abstract
BACKGROUND: In recent years, mesenchymal stem cells (MSCs) have been widely applied in the clinical treatment of knee osteoarthritis (KOA), demonstrating promising therapeutic efficacy. However, intervention protocols for MSCs have not yet been standardized, and evidence regarding the impact of different injection frequencies on the efficacy and safety of MSC treatment in KOA remains limited. OBJECTIVE: This study aims to integrate evidence from conventional and network meta-analyses to evaluate the efficacy and safety of different intervention frequencies (single vs. repeated MSC injections) in the treatment of knee osteoarthritis (KOA). METHODS: A systematic search was conducted in PubMed, Embase, the Cochrane Library, and Web of Science databases up to March 1, 2025. Traditional meta-analysis was performed to assess the efficacy and safety of MSC therapy for KOA, followed by a network meta-analysis (NMA) to evaluate the effectiveness of single versus repeated MSC injections. Outcome measures included WOMAC and VAS scores at 3, 6, and 12 months, as well as the incidence of adverse events (AEs). Traditional meta-analysis and NMA were conducted using Review Manager 5.3 and Stata SE16.0, respectively. RESULTS: A total of 16 RCTs involving 622 patients were included. Traditional meta-analysis showed that MSC therapy significantly improved pain and knee joint function in KOA patients at different time points (3, 6, and 12 months). The results of the network meta-analysis (NMA) indicated that, compared to single MSC injections, repeated MSC injections provided greater improvements in pain and functional scores at 6 and 12 months, demonstrating superior efficacy. However, repeated MSC injections were also associated with a higher incidence of adverse events. CONCLUSIONS: Both single and repeated MSC injections could improve pain and knee joint function in patients with KOA. Compared to single injections, repeated MSC injections may offer superior therapeutic benefits; however, they are associated with a higher incidence of adverse events. In clinical practice, potential side effects of repeated MSC administration must be carefully considered. Future research should focus on large-scale, multicenter, and long-term randomized controlled trials to further validate the efficacy and safety of MSC therapy for KOA.