Rahmadian Rizki, Ariliusra Zikril, Kusuma Kevin Rizki Agung, Ali Hirowati, Raymond Benni, Meksiko Riki
Orthopaedic and Traumatology Division, Department of Surgery, Faculty of Medicine, M. Djamil General Hospital, Universitas Andalas, Padang, Indonesia.
Tissue Bank and Cell Department, M. Djamil General Hospital, Padang, Indonesia.
J Orthop Surg Res. 2025 Aug 30;20(1):812. doi: 10.1186/s13018-025-06190-4.
BACKGROUND: Intra-articular injection of mesenchymal stem cells (MSCs) has emerged as a promising therapy for knee osteoarthritis (OA). However, uncertainty remains regarding the optimal cell dose for maximizing clinical benefit. This systematic review and meta-analysis aimed to evaluate the efficacy of MSC injections for knee OA and investigate the relationship between cell dose and treatment outcome. METHODS: A comprehensive literature search was conducted in PubMed and Scopus for randomized controlled trials (RCTs) published between 2015 and 2025. Eligible studies were RCTs that used intra-articular MSC injections for knee OA, and WOMAC scores were reported at baseline and 12-month follow-up. Standardized mean differences (SMDs) were pooled using a random-effects model. Subgroup analysis and meta-regression were performed to evaluate the effect of MSC dose on treatment outcomes. RESULTS: Eight treatment arms from six RCTs involving 300 patients were included. The pooled SMD in the WOMAC score at 12 months was -1.35 (95% CI: -1.97 to -0.74), indicating a moderate to large treatment effect. MSC doses of ≤ 25 million cells were associated with statistically significant improvement, while higher doses did not demonstrate additional benefit. Meta-regression confirmed no significant dose-response relationship. Heterogeneity was moderate (I2 = 49.8%). CONCLUSION: Intra-articular MSC therapy significantly improves clinical outcomes in knee OA at 12 months, with lower doses (≤ 25 million cells) appearing to be both effective and potentially more efficient. These findings support dose optimization as a critical consideration in advancing MSC therapy.
背景：关节腔内注射间充质干细胞（MSCs）已成为治疗膝关节骨关节炎（OA）的一种有前景的疗法。然而，关于使临床获益最大化的最佳细胞剂量仍存在不确定性。本系统评价和荟萃分析旨在评估MSCs注射治疗膝关节OA的疗效，并研究细胞剂量与治疗结果之间的关系。 方法：在PubMed和Scopus中对2015年至2025年发表的随机对照试验（RCTs）进行全面的文献检索。符合条件的研究为使用关节腔内注射MSCs治疗膝关节OA的RCTs，且报告了基线和12个月随访时的WOMAC评分。采用随机效应模型汇总标准化均数差（SMDs）。进行亚组分析和Meta回归以评估MSCs剂量对治疗结果的影响。 结果：纳入了来自6项RCTs的8个治疗组，共300例患者。12个月时WOMAC评分的汇总SMD为-1.35（95%CI：-1.97至-0.74），表明治疗效果为中度至高度。≤2500万个细胞的MSCs剂量与统计学上的显著改善相关，而更高剂量未显示出额外益处。Meta回归证实无显著的剂量反应关系。异质性为中度（I2 = 49.8%）。 结论：关节腔内MSCs治疗在12个月时显著改善膝关节OA的临床结局，较低剂量（≤2500万个细胞）似乎既有效又可能更高效。这些发现支持将剂量优化作为推进MSCs治疗的关键考虑因素。
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