Organoid‐tissue extracellular vesicles

Abstract Extracellular vesicles (EVs) are lipid bilayer structures secreted by cells that act as intercellular messengers. Tissue‐derived EVs (TEVs), harvested from the tissue interstitium, directly reflect the actual physiological or pathological state of the tissue microenvironment. However, the difficulty in tissue acquisition severely limits the development of TEVs. In contrast, organoids are 3D cell clusters cultured from stem cells, which have spatial structures and physiological functions that are highly similar to the source tissues. Although organoid‐derived EVs (OEVs), isolated from culture supernatants, can reflect complex cellular interactions, they cannot directly reflect the state of the tissue microenvironment like TEVs. Building on the foundation of TEVs and OEVs, we introduce the innovative concept of organoid‐tissue EVs (OTEVs), where residing in the organoid interstitium. Acting as a communication bridge between OEVs and TEVs, OTEVs can accurately represent the true microenvironment. They overcome the challenges associated with the limited availability of TEVs and the inability of OEVs to directly reflect the microenvironment. We believe that OTEVs will synergize with TEVs and OEVs to enhance the understanding of the pathogenesis of complex diseases, as well as to improve their diagnosis and treatment.