Acellular mesenchymal stem cell–derived exosomes and secretome for erectile dysfunction: a systematic review and meta-analysis of preclinical studies
Victor Jeremia Syaropi Simanjuntak, Dimas Sindhu Wibisono, Erlangga Pradipta Harianto, Sean Gerry Santoso, Ishak Andreas Soritua Lumban GaolPurpose:
Phosphodiesterase-5 inhibitors provide symptomatic relief for erectile dysfunction (ED), but patients with neurogenic injury or long-standing diabetes may remain partial or nonresponders. Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs)/exosomes and secretome/conditioned medium (CM) represent potential cell-free restorative therapies. We systematically evaluated their efficacy in preclinical ED models.
Materials and methods:
PubMed and Europe PubMed Central were searched through September 1, 2025, for controlled in vivo rodent studies comparing MSC-derived EVs/exosomes or secretome/CM with model-matched ED controls. Erectile function was assessed using maximal intracavernosal pressure normalized to mean arterial pressure (ICP/MAP). Risk of bias was evaluated using the SYRCLE tool. Standardized mean differences (SMDs) were pooled using random-effects meta-analysis, with subgroup and sensitivity analyses.
Results:
Thirteen studies comprising 18 comparisons (126 treated and 106 control animals) were included. MSC-derived acellular therapies significantly improved erectile function (SMD, 2.17; 95% CI, 1.48–2.87; I² = 70%). Effects were consistent in bilateral cavernous nerve injury and diabetic models. Native and engineered EVs showed no statistically significant subgroup difference. Mechanistic findings supported restoration of NO/cGMP signaling, smooth-muscle preservation, antifibrotic activity, and neuroprotective and antioxidant effects.
Conclusion:
MSC-derived EVs/exosomes and secretome/CM improve erectile function across preclinical ED models, although substantial heterogeneity and methodological reporting limitations reduce certainty. Standardized EV characterization, dosing, and functional assessment are required before clinical translation.