{"title":"来自不同间充质干细胞来源的细胞外囊泡在骨再生中的独特作用：系统综述和荟萃分析。","authors":"Jieying Mai, Yanzhuang Ke, Yufan Yao","doi":"10.62347/WLNC8175","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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<sup>10</sup> 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<sup>2</sup>=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.</p><p><strong>Conclusion: </strong>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<sup>10</sup> particles/kg) and delivery strategies is essential for successful clinical translation.</p>","PeriodicalId":7731,"journal":{"name":"American journal of translational research","volume":"17 8","pages":"5799-5813"},"PeriodicalIF":1.6000,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432756/pdf/","citationCount":"0","resultStr":"{\"title\":\"Distinct roles of extracellular vesicles derived from various mesenchymal stem cell sources in bone regeneration: a systematic review and meta-analysis.\",\"authors\":\"Jieying Mai, Yanzhuang Ke, Yufan Yao\",\"doi\":\"10.62347/WLNC8175\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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<sup>10</sup> 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<sup>2</sup>=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.</p><p><strong>Conclusion: </strong>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<sup>10</sup> particles/kg) and delivery strategies is essential for successful clinical translation.</p>\",\"PeriodicalId\":7731,\"journal\":{\"name\":\"American journal of translational research\",\"volume\":\"17 8\",\"pages\":\"5799-5813\"},\"PeriodicalIF\":1.6000,\"publicationDate\":\"2025-08-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432756/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"American journal of translational research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.62347/WLNC8175\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q3\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"American journal of translational research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.62347/WLNC8175","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q3","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0
摘要
目的：本系统综述和荟萃分析评估了间充质干细胞来源的细胞外囊泡（MSC-EVs）在骨再生中的治疗效果和潜在机制，并基于EV来源、剂量和递送途径进行了亚组分析。方法：综合检索PubMed、Embase和Web of Science（2015-2024）数据库，共检索2414篇文献，其中20篇体内随机对照试验（rct）符合纳入标准。提取动物模型、EV来源、给药、给药方法和结果的数据，包括骨量/总体积、组织学、生物力学。采用随机效应模型进行meta分析和亚组比较。结果：msc - ev显著促进骨再生（合并标准化平均差[SMD]=2.17； 95%可信区间：2.8 -2.25；P10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EV来源的疗效一致。大鼠模型（n=13）的SMD为2.8,rct （n=12）的异质性较低（I2=25%）， SMD为2.9。骨髓驱动的骨髓间充质干细胞- ev （bmscs - ev）在临界尺寸缺陷中表现出优越的成骨潜能；脐带驱动的msc - ev （ucmsc - ev）具有抗炎和骨保护作用；人类诱导的多能干细胞衍生的msc - ev （hips - msc - ev）支持多功能组织修复。敏感性分析证实了结果的稳定性。结论：骨髓间充质干细胞- ev以来源依赖的方式显著促进骨再生：骨髓间充质干细胞- ev在临界尺寸缺损中表现出优越的疗效；ucmsc - ev在炎性骨溶解中有效；hips - msc - ev支持多功能组织修复。优化剂量（≥1×1010颗粒/kg）和给药策略对于成功的临床转化至关重要。
Distinct roles of extracellular vesicles derived from various mesenchymal stem cell sources in bone regeneration: a systematic review and meta-analysis.
Purpose: 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.
Methods: 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.
Results: 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 (≥1×1010 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 (I2=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.
Conclusion: 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 (≥1×1010 particles/kg) and delivery strategies is essential for successful clinical translation.
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