Abstract

Summary: Exosomes are extracellular vesicles released by the vast majority of cell types both in vivo and ex vivo, upon the fusion of multivesicular bodies (MVBs) with the cellular plasma membrane. Two main functions have been attributed to exosomes: their capacity to transport proteins, lipids and nucleic acids between cells and organs, as well as their potential to act as natural intercellular communicators in normal biological processes and in pathologies. From a clinical perspective, the majority of applications use exosomes as biomarkers of disease. A new approach uses exosomes as biologically active carriers to provide a platform for the enhanced delivery of cargo in vivo. One of the major limitations in developing exosome-based therapies is the difficulty of producing sufficient amounts of safe and efficient exosomes. The identification of potential proteins involved in exosome biogenesis is expected to directly cause a deliberate increase in exosome production. In this review, we summarize the current state of knowledge regarding exosomes, with particular emphasis on their structural features, biosynthesis pathways, production techniques and potential clinical applications.

Highlights

  • Extracellular vesicles (EVs) are differently sized vesicles released by the vast majority of cell types both in vivo and ex vivo

  • It is important to determine whether the resulting exosomes are involved in a complex biological rheostat that fine-tunes downstream biological activity, whether these rheostats are modulated by external stimuli and whether genetic modification enhances exosome release or modifies cargo and surface markers to improve their properties or to prevent rejection

  • A sophisticated system called EXOsomal Transfer Into Cells (EXOtic) combining six-transmembrane epithelial antigen of prostate 3 (STEAP3) and a syndecan-4 fragment of L-aspartate oxidase, with other genes involved in exosome biogenesis was recently described [229]

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Summary

Introduction

Extracellular vesicles (EVs) are differently sized vesicles released by the vast majority of cell types both in vivo and ex vivo. Two main functions have been attributed to EVs: (1) their capacity as natural intercellular communicators to transport proteins, lipids and nucleic acids between cells and organs in normal biological processes and (2) their active involvement in the progression of pathologies such as cancer. Based on their size, biogenesis pathways and other biophysical and biochemical criteria, EVs as natural intercellular communicators to transport proteins, lipids and nucleic acids between cells J. 2a0n2s0,i9n, 2n38o0rmal biological processes and (2) their active involvement in the progression2ooff 25 pathologies such as cancer Based on their size, biogenesis pathways and other biophysical and canbiboechgermouicpaledcriintetroiat,wEoVms acianncabteeggorroiueps:edmiicnrtoovetwsioclemsa(iMn Vcsa;te1g0o0r–ie1s0:00mnimcro) vaensdicleexsos(MomVes;s 1(E00X–Os; 30–1100000nnmm))a[n1d–3e]x.osomes (EXOs; 30–100 nm) [1,2,3]. SNARE and syntaxin 5 proteins enable vesicles to dock and fuse with the plasma membrane and to release exosomes into the external medium

Exosome Biogenesis
Regulation and Function
Different Types and Functions of Cells that Release Exosomes
Exosome Manufacturing Status and Challenges
Large Scale Production of Exosomes
High-Quality Uniform Exosomes
Storage Conditions
Quality Control
Treatments for Humans
Conclusions
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