Effects of stem cell–derived exosome therapy on erectile dysfunction: a systematic review and meta-analysis of preclinical studies

INTRODUCTION: Erectile dysfunction (ED) is a common disease among elderly men, and novel therapy methods are needed for drug-refractory ED. As an extracellular vesicle, stem cell–derived exosomes displayed erectile function improvement in rat ED models in some preclinical studies. However, the therapeutic efficacy has not been comprehensively evaluated. AIM: To study the therapeutic effects of stem cell–derived exosomes on ED in preclinical studies and to investigate the potential mechanisms responsible for the efficacy. METHODS: The systematic literature search was conducted in Web of Science, PubMed, and Embase to retrieve studies utilizing stem cell–derived exosomes for ED treatment. We extracted data of intracavernous pressure/mean artery pressure (ICP/MAP), and cavernosum structural changes in rat ED models before and after stem cell-derived exosome therapy. RevMan 5.3 was used to perform meta-analyses of ICP/MAP and cavernosum microstructural changes. Publication bias was assessed with the Egger test and funnel plot by Stata 15.0 (StataCorp). MAIN OUTCOME MEASURES: Outcomes included ICP/MAP, smooth muscle, and endothelial markers—such as the ratio of smooth muscle to collagen and the expression of α-SMA (alpha smooth muscle actin), CD31 (cluster of differentiation 31), nNOS and eNOS (neuronal and endothelial nitric oxide synthase), TGF-β1 (transforming growth factor β1), and caspase 3 protein-to evaluate erectile function and microstructural changes. Forest plots of effect sizes were performed. RESULTS: Of 146 studies retrieved, 11 studies were eligible. Pooled analysis showed that stem cell–derived exosomes ameliorated damaged ICP/MAP (standardized mean difference, 3.68; 95% CI, 2.64-4.72; P < .001) and structural changes, including the ratio of smooth muscle to collagen and the expression of α-SMA, CD31, nNOS, eNOS, TGF-β1, and caspase 3 protein. Subgroup analysis indicated that exosome type and ED model type made no difference to curative effects. CONCLUSION: This meta-analysis suggests the therapeutic efficacy of stem cell–derived exosomes for ED. Exosomes may restore erectile function by optimizing cavernosum microstructures.