Current knowledge on exosome biogenesis and release

Exosomes are nanosized membrane vesicles released by fusion of an organelle of the endocytic pathway, the multivesicular body, with the plasma membrane. This process was discovered more than 30 years ago, and during these years, exosomes have gone from being considered as cellular waste disposal to mediate a novel mechanism of cell-to-cell communication. The exponential interest in exosomes experienced during recent years is due to their important roles in health and disease and to their potential clinical application in therapy and diagnosis. However, important aspects of the biology of exosomes remain unknown. To explore the use of exosomes in the clinic, it is essential that the basic molecular mechanisms behind the transport and function of these vesicles are better understood. Researchers at the Oslo University Hospital have summarized what is presently known about how exosomes are formed and released by cells. Moreover, other cellular processes related to exosome biogenesis and release, such as autophagy and lysosomal exocytosis are presented. Finally, methodological aspects related to exosome release studies are discussed.

Study of exosome release

Exosomes are released after fusion of MVBs with the plasma membrane. Exosomes have a complex composition of protein, nucleic acids, lipids and other metabolites. Due to their small size (<150 nm in diameter), exosomes are best visualized by electron microscopy. Though some commonly used electron microscopy methods artificially show exosomes as cup-shaped structures, exosomes are round structures. Exosomes are isolated from cell-conditioned media by several protocols that aim to concentrate the exosomal signal to be analyzed and to avoid contaminating molecules such as proteins that are secreted by other mechanisms. Once isolated, exosomes can be analyzed by several methods such as the ones included in this figure. TRPS tunable resistive pulse sensing, NTA nanoparticle tracking analysis.