Extracellular vesicles and their application in the diagnosis and treatment of diseases

Extracellular vesicles (EVs) are a kind of heterogeneous vesicles released by essentially all cell types, which plays an important role in intercellular communication and in the regulation of physiological process (or pathology). EVs mainly includes microvesicles (50-1000 nm), apoptotic bodies (50-5000 nm) and exosomes (30-150 nm), based on distinct biogenesis pathways. Microvesicles are formed by direct budding of the plasma membrane, in which ARF6 and RhoA are important regulators. In addition, oncosomes are also a kind of microvesicles, which are specifically released by tumor cells and contain many specific molecules of tumor cells. When cells undergo apoptosis, they could also release a population of EVs called apoptotic bodies. This kind of EVs is formed through outward blebbing and fragmentation of the cell membrane. Exosomes are derived from multivesicular bodies (MVBs), and released by cells upon fusion of MVBs with the plasma membrane. Exosomes have complex formation and regulatory mechanisms, including endosomal sorting complex dependent and non-dependent mechanisms. Many researchers have shown that EVs with different types and different cell sources may have different components and functions. EVs mainly carry the bioactive molecules of donor cells, such as proteins, DNA or RNA, and target nearby or remote cells to perform different biological functions, thus affecting the physiological and pathological processes of recipient cells. Cells can also discharge their waste by EVs. By transporting cargoes to extracellular, EVs can regulate the amount of intracellular cargoes, thus affecting the survival status of cells. This approach can be beneficial to cells (removing harmful substances) or harmful (transporting drugs outside the cell). Secondly, some key molecules in EVs can be regulated by donor cells according to their state. So, EVs can also reflect the state changes of donor cells, and have the potential as a biomarker for the diagnosis and treatment of diseases. Due to their stable existence in body fluids and derived from various tissues of the body, EVs can not only be a new biomarker of liquid biopsy, but also reflect the heterogeneity and the genesis or development of diseases. As a natural endogenous material, EVs can also serve as a potential drug delivery carrier, and have the advantages of low immunogenicity and crossing the blood brain barrier. In addition, EVs have many other applications. For example, they can be an alternative to cells as a therapeutic agent, as well as targets of disease treatment. This review summarizes the following parts: Firstly, biological origin, biological composition, biological characteristics, and biological functions of EVs. Secondly, the isolation and characterization of EVs. Thirdly, the application of EVs in the diagnosis and treatment of diseases were introduced. At present, the heterogeneity, biological composition and the formation mechanism of EVs need to be further studied, so that it can be better applied in the diagnosis and treatment of diseases. The effective isolation method is also necessary for its clinical application. It is believed that with the development of various biological technologies, these problems will be gradually solved, the biological function of EVs will be also clearly understood, and EVs based application in diseases will make new breakthroughs.