Abstract
Extracellular vesicles (EVs) play a crucial role in cell-to-cell communication by transporting functionally active molecules, including proteins, lipids, and nucleic acids. While extensive research has focused on EVs generated from traditional two-dimensional (2D) monolayer cultures (2D-EVs), the emergence of three-dimensional (3D) organoid systems has led to the development of organoid-derived EVs (OEVs), which more closely mimic the physiological conditions of native tissues. In contrast to 2D cultures, 3D systems offer improved EV yield and cargo specificity, enhancing their translational potential. This review discusses the distinctive features of OEVs, including their enhanced tissue relevance, diverse molecular composition, and promising therapeutic applications in areas like disease modeling, regenerative therapies, and targeted drug delivery. We also present an overview of the current organoid-based platforms used to produce OEVs, recent innovations in EV modification and bioengineering, and the practical barriers to their clinical adoption. By comparing the strengths and limitations of OEVs with those of 2D-EVs, we provide a comprehensive perspective on their future role in precision healthcare, biomarker identification, and advanced therapeutic strategies.