Exosomes: Potential Disease Biomarkers and New Therapeutic Targets

Abstract

Exosomes are extracellular vesicles released by cells, both constitutively and after cell activation, and are present in different types of biological fluid. Exosomes are involved in the pathogenesis of diseases, such as cancer, neurodegenerative diseases, pregnancy disorders and cardiovascular diseases, and have emerged as potential non-invasive biomarkers for the detection, prognosis and therapeutics of a myriad of diseases. In this review, we describe recent advances related to the regulatory mechanisms of exosome biogenesis, release and molecular composition, as well as their role in health and disease, and their potential use as disease biomarkers and therapeutic targets. In addition, the advantages and disadvantages of their main isolation methods, characterization and cargo analysis, as well as the experimental methods used for exosome-mediated drug delivery, are discussed. Finally, we present potential perspectives for the use of exosomes in future clinical practice.

Keywords: biogenesis; biomarker; exosome; intercellular communication; therapeutic vehicle.

Figure 1

Biogenesis of exosomes and cell-to-cell communication. (a) Exosome biogenesis starts with the inward budding of the plasma membrane and the participation of proteins, such as clathrin. Endocytosis results in the formation of an early endosome, which encapsulates cellular proteins and genetic material present in the cytoplasm, becoming a late endosome. Then, multivesicular bodies (MVBs) containing exosomes are formed. The generation of exosomes can occur by two main pathways: (1) a ESCRT-dependent pathway and (2) a ESCRT-independent pathway. MVBs can be directed to the lysosome for degradation and recycling of MVB components or to the plasma membrane, and exosomes are released into the extracellular space by Rab small GTPases or R-SNARE. (b) Secreted exosomes can be taken up by recipient cells through several mechanisms, including (1) receptor-ligand interaction, (2) exosomal internalization by endocytosis, phagocytosis or micropinocytosis and (3) direct membrane fusion.