Efficacy and safety of single versus repeated injections of mesenchymal stem cells for the treatment of knee osteoarthritis: a systematic review and network meta-analysis of randomized controlled trials

Relatively higher-quality human studies compared with other topics in this database, e.g. multiple RCTs or systematic reviews. This does not mean it is standard or approved care.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

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

Evidence level

Relatively higher-quality human studies compared with other topics in this database, e.g. multiple RCTs or systematic reviews. This does not mean it is standard or approved care.

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