Abstract

Exosomes are small (∼30–140 nm) lipid bilayer-enclosed particles of endosomal origin. They are a subset of extracellular vesicles (EVs) that are secreted by most cell types. There has been growing interest in exosome research in the last decade due to their emerging role as intercellular messengers and their potential in disease diagnosis. Indeed, exosomes contain proteins, lipids, and RNAs that are specific to their cell origin and could deliver cargo to both nearby and distant cells. As a result, investigation of exosome cargo contents could offer opportunities for disease detection and treatment. Moreover, exosomes have been explored as natural drug delivery vehicles since they can travel safely in extracellular fluids and deliver cargo to destined cells with high specificity and efficiency. Despite significant efforts made in this relatively new field of research, progress has been held back by challenges such as inefficient separation methods, difficulties in characterization, and lack of specific biomarkers. In this review, we summarize the current knowledge in exosome biogenesis, their roles in disease progression, and therapeutic applications and opportunities in bioengineering. Furthermore, we highlight the established and emerging technological developments in exosome isolation and characterization. We aim to consider critical challenges in exosome research and provide directions for future studies.

Highlights

  • Interest in exosome research has increased dramatically in recent years due to their unique functions as intercellular messengers, abilities to alter recipient cell bioactivities, as well as therapeutic potential in disease diagnostics and targeted drug delivery.[1,2,3] Exosomes are a type of extracellular vesicles (EVs) with diameters of 30–140 nm and are secreted from most cell types into the extracellular space after fusion of multivesicular bodies (MVBs) with the cell membrane.[4]

  • This review aims to summarize the current knowledge on exosome biogenesis and biological functions, as well as existing applications in therapy and emerging techniques in exosome characterization and isolation

  • Prior to implementation of any diagnostic practice, a complete database of the exosomal profiles seen in diseases should be compiled to prevent misdiagnosis due to similar cargo contents, and technologies must be developed for a clinical setting

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Summary

INTRODUCTION

Interest in exosome research has increased dramatically in recent years due to their unique functions as intercellular messengers, abilities to alter recipient cell bioactivities, as well as therapeutic potential in disease diagnostics and targeted drug delivery.[1,2,3] Exosomes are a type of extracellular vesicles (EVs) with diameters of 30–140 nm and are secreted from most cell types into the extracellular space after fusion of multivesicular bodies (MVBs) with the cell membrane.[4] Alongside exosomes, cells secrete other types of EVs including apoptotic bodies (50–500 nm; released during apoptosis) and ectosomes (30–100 nm; assembled and released directly from the plasma membrane).[1,5,6,7] Some of these EVs are similar to exosomes in their physical properties such as size and density, which makes isolating exosomes quite challenging.[8] The primary difference among the various EVs is thought to be their particular mode of biogenesis, which in turn determines the cargo contents and functions.[5] Non-exosomal EVs result from direct. We hope to point out directions for future studies

BIOGENIC PATHWAY
ESCRT-mediated pathway
ESCRT-independent pathway
Loading mechanisms and cargo
Transport and release
Exosomes as biomarkers
EXOSOMES AND CANCER
Exosomes facilitating tumor proliferation and altering the microenvironment
Exosomes and metastasis
Exosomes and cancer immune systems
EXOSOME-BASED THERAPEUTIC OPPORTUNITIES
Inhibit disease derived exosomes
Using exosomes as therapeutic platforms
Exosomes as gene carriers
Exosomes as drug delivery carriers
ISOLATION
Established protocols
By density
Method of Protocols isolation
By size
By function
Emerging—Isolation platforms
Nanowire trapping
Isolation by function
CHARACTERIZATION
Size and shape
Molecular profiling
Proteomics and lipidomics
Genomics
Microscopy and nanoscopy for exosome imaging
Direct post-isolation labelling for imaging
Genetic tagging by fluorescent proteins
Advanced fluorescent microscopy technique
CONCLUSIONS
Findings
Methods
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