From bench to bedside: the promise and roadblocks of extracellular vesicle therapeutics

Extracellular vesicles (EVs) have transformed the landscape of precision therapeutics, owing to their intrinsic biocompatibility, capacity to transport biomolecules, and ability to cross biological barriers. Benefiting from these advantages, several EV-based therapeutic applications are currently under active development. However, most products remain at the preclinical stage due to significant translational challenges. In this review, we systematically outline these obstacles and highlight opportunities that can accelerate the clinical translation of EVs. We first identify core issues impeding clinical progress, such as difficulties in isolation, storage stability, precise characterization, biosafety evaluation, and quality control. After that, we examine emerging technologies designed to overcome these bottlenecks, including advanced bioreactors for large-scale production, microfluidic systems for high-purity separation, single-vesicle analysis technologies to address heterogeneity, and machine learning approaches that enhance standardization and support clinical decision-making. Finally, we discuss future directions focused on standardizing EV production, improving safety assessment, and ensuring regulatory compliance. By addressing current challenges and identifying promising pathways, this review aims to facilitate the translation of EV-based therapies from bench to bedside.