Salivary exosomes: properties, medical applications, and isolation methods

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Salivary exosomes: properties, medical applications, and isolation methods Behzad Cheshmi1   · Hamid Cheshomi2  Received: 18 March 2020 / Accepted: 8 July 2020 © Springer Nature B.V. 2020

Abstract Salivary exosomes are extracellular vesicles (EVs) with abundant CD63 immunoreactivity on their surface. Based on their size and protein composition, these exosomes can be categorized into two classes of exosomes I (mean diameter of 83.5 nm) and II (mean diameter of 40.5 nm). We have attempted to review the features of these exosomes, including origin, composition, separation methods, and their application in medicine. Not only the composition of salivary exosomes is invaluable in term of diagnosis, but can also afford an understanding in roles of the contents and components of these exosomes in the fundamental pathophysiologic processes of different diseases. since these EVs can cross the epithelial barriers they may be essential for transporting of multifarious components from the blood into saliva. Thus, in comparison to other bodily fluids, salivary exosomes are probably a better and accessible tool to examine the function of exosomes in the diagnosis and treatment of disease. Keywords  Saliva · Extracellular vesicles · Exosome · Salivary exosome · Biomarker Abbreviations EV Extracellular vesicle EM Electron microscopy MVB Multivesicular body ESCRT​ Endosomal sorting complexes required to transport ILV Intraluminal vesicle ncRNA Non-coding RNA mtDNA Mitochondrial DNA ssDNA Single-strand DNA RAB Ras associated binding protein ARF ADP ribosylation factor TSG101 Tumor susceptibility gene 101 HSP70 Heat shock protein DRPLA Dentatorubro pallidoluysian atrophy pIgR Polymeric Ig receptor * Hamid Cheshomi [email protected] Behzad Cheshmi [email protected] 1



Faculty of Dentistry, Boroujerd Islamic Azad University, Boroujerd, Iran



Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, P.O. Box 9177948974, Mashhad, Iran

2

Introduction Saliva is a highly diluted fluid consisting of over 99% water; yet, it is not considered an ultrafiltrate of plasma [1]. The composition of saliva is not constant and is related to the circadian rhythm [1]. Saliva consists of different types of electrolytes: namely, sodium, potassium, calcium, magnesium, bicarbonate, and phosphate. Additional salivary compounds include immunoglobulins (Igs), proteins, enzymes, mucins, and nitrogenous products like urea and ammonia [2, 3]. Since the composition of saliva—in addition to oral structures—is affected by systemic circulation, the substances within saliva have come to be regarded as a source for diagnosing different diseases [4, 5]. Two pathways are suggested to describe the correlation between saliva and blood [6]. In the first pathway, plasma elements influence salivary glands, resulting in synthesized surrogate endpoints. This point of view has gained support [7], forming the basis of “-omics” research in saliva. The other pathway posits that systemic constituents appear in saliva by crossing