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 alpha-SMA (alpha smooth muscle actin), CD31 (cluster of differentiation 31), nNOS and eNOS (neuronal and endothelial nitric oxide synthase), TGF-beta 1 (transforming growth factor beta 1), 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 alpha-SMA, CD31, nNOS, eNOS, TGF-beta 1, 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.