Nanoscale therapeutics for erectile dysfunction: a meta-analysis of stem cell-derived extracellular vesicles as natural nanoparticles in diabetic rat models.

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSION

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.