Exosomes - novel tools in diagnostics and treatments

Written by: Vujic Vesna and Volnermanis Baraks

Supervisor: Dr. Gergely Jócsák

Physiology Department, University of Veterinary Medicine, Budapest

Introduction

Exosomes are a subtype of extracellular vesicles that are membrane-derived, they are formed as a result of a selective intracellular process in which plasma membrane lipoproteins are placed within endosomes, later to be released into the extra cellular space. They exist and are secreted from almost all cell types in the body, both prokaryotic and eukaryotic (Johnstone, 2006).

Théry et al (2002) stated that despite their similarity, exosomes differ from microvesicles in the fact that they are secreted only from living cells, whereas microvesicles can be produced from cells which have undergone apoptosis. In addition, contrary to microvesicles that bud from the plasma membrane, exosomes are released from the cell following a fusion between multi vesicular bodies with the cell plasma membrane (Skotland et al, 2019).

Being part of the cellular secretome, exosomes transfer cellular constituents (DNA, mRNA, lipids, proteins) extracellularly in a paracrine fashion to a nearby cell or, alternatively in a systemic fashion - travel through the blood stream to reach a more distant cell. Exosomes possess various additional attributes, such as the ability to penetrate the blood-brain barrier, avoid inducing any response of the immune system and withstand degradation of any enzymes (Sarko and McKinney, 2017). A recent study by Jeppesen et al (2019) has compared ‘classical exosomes’ (containing tetraspanins CD63, CD81, or CD9) and ‘non-classical exosomes’ (do not contain the mentioned tetraspanins). This study showed that ‘classical exosomes’ do not contain DNA and are not the mechanisms for active DNA release as previously believed. However, exosomes do contain RNA and RNA binding proteins.

Current research work is aimed at thoroughly understanding the way cells communicate with each other. Exosomal attributes mentioned beforehand are the reason why one of the main fields focuses at utilizing exosomes as a natural delivery vehicle system for therapeutic drugs to different cells (Sarko and McKinney, 2017).

Biogenesis

Exosomes are believed to originate from multivesicular bodies (MVB), a type of endosomes that contains membrane-bound intraluminal vesicles (ILV). ILVs form inside the MVBs by budding into their lumen. Once formed, MVBs can either undergo degradation by fusing with lysosomes or be released as exosomes to the extracellular environment by fusing with the cytoplasmic side of the plasma membrane of the cell (Sarko and McKinney, 2017).

Henne et al (2011) showed that endosomal sorting complex transport (ESCRT) mechanism has an important role in the formation process of ILVs, facilitation of MVB formation, vesicle budding, and exosomal cargo sorting into MVBs. However, a review by Zhang et al (2019) stated that the cargo sorting process can be ESCRT-independent as well, depending on the origin of the cell type.

Structure and chemical content

Structure

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Chemical content

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Methods of exosome extraction

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Ultracentrifugation

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Ultrafiltration

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Size-exclusion liquid chromatography

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Precipitation

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Immunoaffinity techniques

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Microfluidics-based isolation techniques

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Exosomes as a diagnostic tool

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Biomarkers

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Therapeutics

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References

Articles

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Patents

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Figures

All the figures have been taken from open access articles

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