Organoid-derived extracellular vesicles: recent advances and therapeutic applications

Extracellular vesicles (EVs) are crucial mediators of intercellular communication, transporting biologically active materials such as proteins, lipids, and nucleic acids. Although EVs derived from 2-dimensional (2D) monolayer cell cultures (2D-EVs) have been extensively studied, recent advancements in 3-dimensional (3D) organoid technology have enabled the generation of organoid-derived EVs (OEVs), which more closely replicate native tissue environments. The 2D culture system has significant limitations for EV production, including low yield and limited enrichment of therapeutic cargo, thereby restricting clinical translation compared to 3D-EVs. This review explores how OEVs provide enhanced tissue specificity, greater molecular complexity, and superior therapeutic potential, particularly in disease modeling, regenerative medicine, and drug delivery. Here, we outline various organoid platforms used to produce OEVs and highlight their potential therapeutic applications. Additionally, we examine recent advances in EV engineering, biofabrication techniques, and the translational challenges related to clinical implementation. By critically assessing the advantages and limitations of OEVs relative to 2D-EVs, this review offers key insights into their potential roles in precision medicine, biomarker discovery, and next-generation therapeutics.