Molecular Neuropathology Department, Centro de Biologia Molecular Severo Ochoa-CSIC Madrid, Spain/p>
Received Date: May 22, 2017; Accepted Date: June 05, 2017; Published Date: June 11, 2017
Citation: Guix FX. The Potential Use of Exosomes as a Diagnostic and Prognostic Tool. J Biomedical Sci. 2017, 6:3. doi: 10.4172/2254-609X.100068
Copyright: © 2017 Guix FX, This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Cells release distinct types of extracellular vesicles (EV). EVs are lipid bilayer enclosed membrane vesicles ranging from 40 nm to 5,000 nm in diameter. Depending on the pathways responsible for their biogenesis, EVs can be classified as apoptotic bodies, microvesicles and exosomes [1,2]. Apoptotic bodies are generated from the fragmentation of the cell membrane of apoptotic cells , while microvesicles are originated at the plasma membrane by ontward blebbing and have a size ranging from 100 to 1000 nm . On the other hand, exosomes are released after fusion of multivesicular bodies (MVBs) with the plasma membrane. MVBs are formed during the maturation of endosomes after the invagination of the endosomal membrane towards the lumen and consecutive scission, giving rise to intraluminal vesicles (ILVs). ILVs are named exosomes after being released to the extracellular space and have a size ranging from 50 to 100 nm . EVs contain proteins, lipids and RNAs and are suggested to play different roles, from cell-to-cell communication to removal of misfolded proteins and tissue development 005B3].
Independently of their biological function, there is an increasing interest in using exosomes in clinic as biomarkers of several pathological conditions due to several reasons. Because of their intracellular origin, exosomes work as reporters of the biochemical changes occurring in many diseases, such as cancer, neurological or immunological conditions. Many groups managed to isolate a cell-specific population of exosomes from the blood of patients [4-11] what would allow physicians to monitor in real time the status of a patient or the efficacy of a medication by simply taking a blood sample and analyzing the content of exosomes from a specific cell-type. In addition, blood draws are carried out daily in clinical practice and they have low cost in comparison to other diagnostic methods. Blood draws are also less invasive than other diagnostic approaches (e.g. biopsies).
Different methods have been developed to isolate a specific population of exosomes from blood in order to analyze their content. The antibody-based methods use a capture antibody against an exosomal marker, either coupled to streptavidin or magnetic beads [8,11], coated on the wells of an ELISA plate  or used in flow cytometry separation . For example, circulating glypican 1-bearing exosomes have been isolated by flow cytometry and were shown to be diagnostic for early and late pancreatic cancer . Another example is the use of ELISA plates coated with an anti-CD63 antibody to capture circulating exosomes from the plasma of patients with breast cancer. When combined with a detection antibody against Del-1 protein it showed useful for diagnosis of breast cancer . Also, neural exosomes from human plasma isolated with superparamagnetic microbeads coated with anti-L1CAM antibody showed higher levels of synuclein in patients with Parkinson’s disease .
On the other hand, some studies combine the precipitation of vesicles from a biological fluid by means of a chemical agent (e.g. Exoquick) with an antibody-based approach [5,6]. Using this method, it was possible to discriminate between controls and AD patients by determining the levels of Aβ42 and certain phospho-specific tau species (p181 and p396) in blood-derived neural exosomes (exosomes can go across the blood brain barrier).
Differential centrifugation has also been used to isolate TGFβ and MAGE 3/6-positive exosomes from the plasma of patients with ovarian carcinoma . Finally, new and more sophisticated methods are being developed, and could be incorporated in the daily clinical practice as screening procedures for certain diseases in the near future. For example, Shao et al., showed that blood can be analyzed by a microfluidic chip-based detection method to monitor patients with glioblastoma, combining a CD63 antibody-based capture approach with a miniaturized nuclear magnetic resonance system .
In summary, blood-derived exosomes may become a useful diagnostic and prognostic tool for physicians. They can be obtained by low-invasive means and may become part of the daily clinical practice to diagnose or monitor patients in the near future.