Abstract
Extracellular vesicles (EVs) have various advantageous properties, including a small size, high biocompatibility, efficient cargo loading, and precise cell targeting ability, making them promising tools for therapeutic development. EVs have been increasingly explored for applications like drug delivery. However, due to limited cellular secretion rates of EVs, wide-scale clinical applications are not achievable. Therefore, substantial strategies and research efforts have been devoted to increasing cellular secretion rates of EVs. This review describes various studies exploring different methods to increase the cellular production of EVs, including the application of electrical stimulus, pharmacologic agents, electromagnetic waves, sound waves, shear stress, cell starvation, alcohol, pH, heat, and genetic manipulation. These methods have shown success in increasing EV production, but careful consideration must be given as many of these strategies may alter EV properties and functionalities, and the exact mechanisms causing the increase in cellular production of EVs is generally unknown. Additionally, the methods' effectiveness in increasing EV secretion may diverge with different cell lines and conditions. Further advancements to enhance EV biogenesis secretion for therapeutic development is still a significant need in the field.