Lou Kecheng, Hu Junjie, Tong Jiayue, Wang Zhanshi
Department of Urology, Lanxi People's Hospital, Jinhua, Zhejiang, China.
Dpartment of Urology, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, China.
Stem Cell Res Ther. 2025 Jun 2;16(1):278. doi: 10.1186/s13287-025-04389-0.
Erectile dysfunction (ED), a prevalent male sexual disorder, severely impacts quality of life. Extracellular vesicles (EVs), natural nanoparticles (30-200 nm) secreted by stem cells, represent a novel nanomedicine platform for ED treatment due to their ability to encapsulate bioactive cargo (e.g., miRNAs, proteins) and target damaged tissues. Stem cell-derived extracellular vesicles (SC-EVs) have emerged as a promising therapeutic strategy for multiple diseases. This meta-analysis evaluates the therapeutic efficacy of SC-EVs in rat ED models and explores their translational potential.
We systematically searched PubMed, Embase, Cochrane Library, and Web of Science for studies published up to December 2024. Randomized controlled trials (RCTs) assessing EVs in ED treatment were included. A random-effects model was applied to account for between-study heterogeneity, with standardized mean differences (SMDs) and 95% confidence intervals (CIs) calculated for continuous outcomes.
Twenty studies involving 324 rats were included. EVs significantly improved erectile function (SMD = 4.19, 95% CI: 3.31-5.08, P < 0.00001). Subgroup analyses revealed no significant differences between EV sources (e.g., mesenchymal stem cells [MSCs] vs. adipose-derived stem cells [ADSCs], P > 0.05) or disease models (diabetes mellitus [DM] vs. cavernous nerve injury [CNI], P > 0.05). EVs upregulated the expression of nitric oxide synthase isoforms (nNOS and eNOS), increased smooth muscle content (α-SMA), and improved smooth muscle-to-collagen ratios (P < 0.00001 for all). Funnel plot asymmetry and Egger's test (P < 0.05) indicated publication bias, but trim-and-fill analysis confirmed robust results post-adjustment.
SC-EVs demonstrate significant therapeutic potential for ED in rat models, particularly in restoring vascular and neural integrity. However, limitations include small sample sizes and short follow-up periods. Future research should prioritize clinical translation, mechanistic exploration, and standardized EV production protocols.
勃起功能障碍（ED）是一种常见的男性性功能障碍，严重影响生活质量。细胞外囊泡（EVs）是干细胞分泌的天然纳米颗粒（30 - 200纳米），由于其能够包裹生物活性物质（如微小RNA、蛋白质）并靶向受损组织，代表了一种用于治疗ED的新型纳米医学平台。干细胞衍生的细胞外囊泡（SC-EVs）已成为治疗多种疾病的一种有前景的治疗策略。本荟萃分析评估了SC-EVs在大鼠ED模型中的治疗效果，并探讨了它们的转化潜力。
我们系统检索了截至2024年12月发表在PubMed、Embase、Cochrane图书馆和Web of Science上的研究。纳入评估EVs在ED治疗中的随机对照试验（RCTs）。应用随机效应模型来考虑研究间的异质性，对连续结局计算标准化均值差（SMDs）和95%置信区间（CIs）。
纳入了20项涉及324只大鼠的研究。EVs显著改善了勃起功能（SMD = 4.19，95% CI：3.31 - 5.08，P < 0.00001）。亚组分析显示，EV来源（如间充质干细胞[MSCs]与脂肪来源干细胞[ADSCs]，P > 0.05）或疾病模型（糖尿病[DM]与海绵体神经损伤[CNI]，P > 0.05）之间无显著差异。EVs上调了一氧化氮合酶亚型（nNOS和eNOS）的表达，增加了平滑肌含量（α-SMA），并改善了平滑肌与胶原蛋白的比例（所有P < 0.00001）。漏斗图不对称性和Egger检验（P < 0.05）表明存在发表偏倚，但剪补分析证实调整后结果可靠。
SC-EVs在大鼠模型中显示出对ED具有显著的治疗潜力，特别是在恢复血管和神经完整性方面。然而，局限性包括样本量小和随访期短。未来的研究应优先进行临床转化、机制探索和标准化的EV生产方案。
