Biology, Pathophysiological Role, and Clinical Implications of Exosomes: A Critical Appraisal

Abstract

Exosomes are membrane-enclosed entities of endocytic origin, which are generated during the fusion of multivesicular bodies (MVBs) and plasma membranes. Exosomes are released into the extracellular milieu or body fluids; this process was reported for mesenchymal, epithelial, endothelial, and different immune cells (B-cells and dendritic cells), and was reported to be correlated with normal physiological processes. The compositions and abundances of exosomes depend on their tissue origins and cell types. Exosomes range in size between 30 and 100 nm, and shuttle nucleic acids (DNA, messenger RNAs (mRNAs), microRNAs), proteins, and lipids between donor and target cells. Pathogenic microorganisms also secrete exosomes that modulate the host immune system and influence the fate of infections. Such immune-modulatory effect of exosomes can serve as a diagnostic biomarker of disease. On the other hand, the antigen-presenting and immune-stimulatory properties of exosomes enable them to trigger anti-tumor responses, and exosome release from cancerous cells suggests they contribute to the recruitment and reconstitution of components of tumor microenvironments. Furthermore, their modulation of physiological and pathological processes suggests they contribute to the developmental program, infections, and human diseases. Despite significant advances, our understanding of exosomes is far from complete, particularly regarding our understanding of the molecular mechanisms that subserve exosome formation, cargo packaging, and exosome release in different cellular backgrounds. The present study presents diverse biological aspects of exosomes, and highlights their diagnostic and therapeutic potentials.

Keywords: diseases; exosomes; extracellular transport; secretory vesicles; stem cells.

Figure 1

Exosome biogenesis. The process starts with an invagination of the endosomal membrane, and involves Rab GTPase and endosomal sorting complexes required for transport (ESCRTs). The delivery of cargo to recipient cells occurs via ligand–receptor interactions between the exosome and the host cell.

Figure 2

Structure of an exosome. Exosomes exhibit a complex lipid-bilayer surface structure characterized by an array of surface-localized proteins and membranous lipids, which mediate specific targeting and promote cellular uptake.