Exosomes are nanometer-sized biovesicles that are released into surrounding body fluids after the fusion of the multivesicular bodies and the plasma membrane. They have been shown to contain specific amounts of proteins, lipids and genetic material for each cell, and can be selectively absorbed by neighboring or distant cells far from release, reprogramming the recipient cells based on their bioactive compounds. Therefore, the regulated formation of exosomes, the specific composition of their cargo and the specificity to target cells are of immense biological interest, considering the very high potential of exosomes as non-invasive diagnostic biomarkers, as well as as therapeutic nanocarriers.
In the present review, we describe and analyze recent advances in the elucidation of the regulatory mechanisms of exosome biogenesis, the molecular composition of exosomes, and the technologies used in exosome research
.In addition, we focus on the potential use of exosomes as valuable diagnostic and prognostic biomarkers for their specific cell lineage content and state, and on possibilities as therapeutic vehicles for drug and gene delivery. Exosome research is taking its first steps. A thorough understanding of the subcellular components and mechanisms involved in the formation of exosomes and in the selection of specific cells will shed light on their physiological activities. It is also important to observe if in vitro and in vivo studies have been conducted on the same mechanism and if their conclusions are consistent.
The ESCRT mechanism is initiated by the recognition and sequestration of ubiquitinated proteins in specific domains of the endosomal membrane through subunits of ESCRT-0 that bind to the ubiquitin. Despite the controversy over whether exosome release is a mechanism regulated by ESCRT, different components of ESCRT and ubiquitinated proteins have already been identified in exosomes isolated from several cell types. These four cell types use exosomes to promote EMT, tumor metastasis and drug resistance through a variety of mechanisms. As is evident, the mechanisms of biogenesis and secretion of exosomes are heterogeneous, and the main ESCRT route is secondary to other mechanisms related to lipid rafts and tetraspanins.
The invagination of the membrane associated with the lipid raft is one of the main endocytic mechanisms to shift the load to the primitive endosome (fig. These studies indicate that exosome-mediated lncRNA transfer is an important mechanism that exists in tumor development and plays a crucial role in regulating the tumor microenvironment by influencing major cellular pathways. The specific mechanisms by which exosomes exosomes exert their effects include anti-inflammatories, antioxidants, anti-apoptotics, the promotion of cell proliferation, the ability to transport various substances, etc. Curiously, it is now recognized that exosomes with a specific cellular charge of proteins, lipids and nucleic acids can act as a new mechanism of intercellular communication.
Exosomes derived from bone marrow-derived mesenchymal stem cells promote retinal ganglion cell survival through miRNA-dependent mechanisms. Apparently, there are several specialized mechanisms to ensure the specific classification of bioactive molecules in exosomes, whether the mechanism dependent or independent of ESCRT (in which tetraspanins and lipids are involved), can act in a variety of ways depending on the origin of the cell type.
