Mai Jieying, Ke Yanzhuang, Yao Yufan
Department of Ophthalmology, Sanya Central Hospital Sanya 572000, Hainan, China.
Department of General Surgery (Section Two), Sanya Central Hospital Sanya 572000, Hainan, China.
Am J Transl Res. 2025 Aug 15;17(8):5799-5813. doi: 10.62347/WLNC8175. eCollection 2025.
This systematic review and meta-analysis evaluated the therapeutic efficacy and underlying mechanisms of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) in bone regeneration, with subgroup analyses based on EV source, dose, and delivery route.
A comprehensive search of PubMed, Embase, and Web of Science (2015-2024) identified 2,414 records, of which 20 in vivo randomized controlled trials (RCTs) met the inclusion criteria. Data on animal models, EV sources, dosing, administration methods, and outcomes - including bone volume/total volume, histology, biomechanics - were extracted. Meta-analyses and subgroup comparisons were conducted using random-effects models.
MSC-EVs significantly promoted bone regeneration (pooled standardized mean difference [SMD]=2.17; 95% confidence interval: 2.08-2.25; P<0.00001). Local administration (n=15) and high-dose regimens (≥1×10 particles/kg; n=16) were both effective (SMD=2.16 and 2.11, respectively). Subgroup analyses revealed consistent efficacy across EV sources. Rat models (n=13) yielded an SMD of 2.8, and RCTs (n=12) showed low heterogeneity (I=25%) with an SMD of 2.9. Bone marrow-drived MSC-EVs (BMSC-EVs) exhibited superior osteogenic potential in critical-size defects; umbilical cord-drived MSC-EVs (UCMSC-EVs) showed anti-inflammatory and osteoprotective properties; and human-induced pluripotent stem cell-derived MSC-EVs (hiPS-MSC-EVs) supported multifunctional tissue repair. Sensitivity analyses confirmed result stability.
MSC-EVs significantly enhance bone regeneration in a source-dependent manner: BMSC-EVs demonstrate superior efficacy in critical-size defects; UCMSC-EVs are effective in inflammatory osteolysis; hiPS-MSC-EVs support multifunctional tissue repair. Optimizing dosing (≥1×10 particles/kg) and delivery strategies is essential for successful clinical translation.
本系统评价和荟萃分析评估了间充质干细胞衍生的细胞外囊泡（MSC-EVs）在骨再生中的治疗效果及其潜在机制，并根据细胞外囊泡来源、剂量和递送途径进行了亚组分析。
全面检索PubMed、Embase和Web of Science（2015 - 2024年），共识别出2414条记录，其中20项体内随机对照试验（RCT）符合纳入标准。提取有关动物模型、细胞外囊泡来源、剂量、给药方法和结果的数据，包括骨体积/总体积、组织学、生物力学等。使用随机效应模型进行荟萃分析和亚组比较。
MSC-EVs显著促进骨再生（合并标准化均数差[SMD]=2.17；95%置信区间：2.08 - 2.25；P<0.00001）。局部给药（n = 15）和高剂量方案（≥1×10颗粒/kg；n = 16）均有效（SMD分别为2.16和2.11）。亚组分析显示不同细胞外囊泡来源的疗效一致。大鼠模型（n = 13）的SMD为2.8，RCT（n = 12）显示异质性较低（I = 25%），SMD为2.9。骨髓来源的MSC-EVs（BMSC-EVs）在临界尺寸缺损中表现出卓越的成骨潜力；脐带来源的MSC-EVs（UCMSC-EVs）具有抗炎和骨保护特性；人诱导多能干细胞来源的MSC-EVs（hiPS-MSC-EVs）支持多功能组织修复。敏感性分析证实了结果的稳定性。
MSC-EVs以来源依赖的方式显著增强骨再生：BMSC-EVs在临界尺寸缺损中显示出卓越疗效；UCMSC-EVs对炎性骨溶解有效；hiPS-MSC-EVs支持多功能组织修复。优化剂量（≥1×10颗粒/kg）和递送策略对于成功的临床转化至关重要。
