Emerging Roles of Exosomes in Normal and Pathological Conditions: New Insights for Diagnosis and Therapeutic Applications

Abstract

From the time when they were first described in the 1970s by the group of Johnstone and Stahl, exosomes are a target of constant research. Exosomes belong to the family of nanovesicles which are of great interest for their many functions and potential for diagnosis and therapy in multiples diseases. Exosomes originate from the intraluminal vesicles of late endosomal compartments named multivesicular bodies and the fusion of these late endosomes with the cell membrane result in the release of the vesicles into the extracellular compartment. Moreover, their generation can be induced by many factors including extracellular stimuli, such as microbial attack and other stress conditions. The primary role attributed to exosomes was the removal of unnecessary proteins from the cells. Now, several studies have demonstrated that exosomes are involved in cell–cell communication, even though their biological function is not completely clear. The participation of exosomes in cancer is the field of microvesicle research that has expanded more over the last years. Evidence proving that exosomes derived from tumor-pulsed dendritic cells, neoplastic cells, and malignant effusions are able to present antigens to T-cells, has led to numerous studies using them as cell-free cancer vaccines. Because exosomes derive from all cell types, they contain proteins, lipids, and micro RNA capable of regulating a variety of target genes. Much research is being conducted, which focuses on the employment of these vesicles as biomarkers in the diagnosis of cancer in addition to innovative biomarkers for diagnosis, prognosis, and management of cardiovascular diseases. Interesting findings indicating the role of exosomes in the pathogenesis of several diseases have encouraged researchers to consider their therapeutic potential not only in oncology but also in the treatment of autoimmune syndromes and neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease, in addition to infectious diseases such as tuberculosis, diphtheria, and toxoplasmosis as well as infections caused by prions or viruses such as HIV. The aim of this review is to disclose the emerging roles of exosomes in normal and pathological conditions and to discuss their potential therapeutic applications.

Characteristics of exosomes andmicroparticles discovered in human tears

“…Экзосомы формируются путём впячивания внутрь мембраны мультивезикулярных телец (МВТ, поздних эндосом), захватывая при этом участок цитозоля, накапливаются в полости МВТ и высвобождаются из клеток при слиянии мембраны МВТ с плазмалеммой. Экзосомы найдены во всех исследованных жидкостях тела [3,4], а их способность к адресной доставке молекулярных сигналов к клеткам-реципиентам служит основой для многочисленных исследований роли экзосом в функционировании организма и в патогенезе различных заболеваний [2,5].Заболевания органа зрения также привлекают внимание исследователей экзосом: показано их присутствие в водянистой влаге [6], а исследования экзосом, продуцирумых клетками трабекулярного аппарата глаза, установили присутствие в этих структурах маркеров глаукомы [7]. Экзосомы продуцируются пигментными клетками сетчатки в культуре, и авторы полагают, что они вовлечены в патогенез возрастной дегенерации макулы [8].…”

Uptake of lymphoma-derived exosomes by peripheral blood leukocytes

“…47 Cancer cells in particular secrete large quantities of TEXs, which can be found in peripherally circulating blood. 48 Consequently, blood cells are exposed to many exosomes from both normal and malignant cells, 49 which play key roles in modulating the immune system. 8 While previous studies have investigated exosomal interactions with leukocytes in lymphoid organs, such as APCs in the spleen 50 and follicular dendritic cells (DCs) in the lymph nodes, 51,52 there is less work done regarding uptake of exosomes by peripheral blood cell populations.…”

Quantitative body fluid proteomics in medicine — A focus on minimal invasiveness

“…Alterations in EV protein levels observed in pathological conditions make exosomes a good source for biomarker investigations [207]. More than 35000 proteins were found in the extracellular vesicles (http://www.microvesicles.org/) and using quantitative proteomics techniques 32 potential biomarkers for bladder and prostate cancer, kidney diseases, deep vein thrombosis and brain tumors were identified in body fluids.…”