Extracellular vesicles in erectile dysfunction: a narrative review of multicellular regulation.

BACKGROUND AND OBJECTIVE: Erectile dysfunction (ED) is a multifactorial disorder involving vascular, neural, smooth muscle, and stromal dysfunction. Currently available treatments only provide symptomatic relief without addressing underlying tissue damage. Extracellular vesicles (EVs) act as mediators of intercellular communication involved in tissue repair. This review aims to summarize current evidence on EVs in ED, with a focus on their roles in multicellular regulation and therapeutic applications. METHODS: The PubMed database was reviewed to identify relevant experimental and translational studies on EVs in ED. Studies were included if they focused on EV sources, cargo composition, and their roles in intercellular communication and tissue remodeling. KEY CONTENT AND FINDINGS: EVs derived from multiple cellular sources, including endothelial cells, smooth muscle cells, fibroblasts, pericytes, and stem/progenitor cells, modulate interconnected processes involving vascular regulation, neurovascular signaling, smooth muscle maintenance, stromal remodeling, fibrosis, and oxidative stress. Preclinical studies consistently demonstrate functional improvement across diabetic, neurogenic, and aging-related ED models through enhancement of angiogenesis, neuroregeneration, anti-apoptotic signaling, and fibrosis modulation. However, therapeutic outcomes vary according to EV origin, cargo composition, isolation methods, and delivery strategies, and current evidence remains largely limited to small animal models without standardized protocols or long-term clinical validation. CONCLUSIONS: EVs regulate multicellular communication within the erectile tissue. Despite encouraging preclinical findings, challenges such as heterogeneity, lack of standardization, and limited clinical validation remain. Further advances in precision and mechanism-based EV strategies may help define the therapeutic potential of EV-based approaches in ED.