Current application of exosomes in medicine

Abstract

Exosomes belong to structures called extracellular vesicles (EVs). These spherical units, secreted by most eukaryotic cells, attracted significant interest among researchers in recent years. Exosomes undergo secretion from almost all types of mammalian cells, including dendritic cells, B cells, epithelial cells, mastocytes, reticulocytes, platelets, T cells, mesenchymal stem cells, adipocytes, bone marrow-derived stem cells, embryonic stem cells, fibroblasts, cardiac myocytes, endothelial cells, oligodendrocytes, astrocytes, microglia, neurons, neural stem cells, hepatocytes, lung spheroid cells, as well as tumor cells. Exosomes have several features that enable many methods of their isolation from biological material. Furthermore, physicochemical properties such as size, mass, density, or the ability to interact with specific proteins allowed for the development and advance of several effective methods. Work on exosomes’ recovery and purity made it possible to most effectively determine their isolation methods’ efficiency and accuracy. A common ground for the researchers’ interest in exosomal analyses is the role of exosomes as carriers of disease biomarkers. It has been suggested that exosomes can be used in vaccine development and other immunological-related purposes, as one of their characteristics is the ability to present antigens. Moreover, exosomes have a long half-life. As the human body does not perceive them as foreign bodies, they can penetrate cell membranes and target specific cells, making them even better candidates for the applications mentioned above. Therefore, the following review deals with the nature of exosomes, as well as various methods of their isolation and use in medicine.Running title: Current application of exosomes in medicine

A guide to mass spectrometric analysis of extracellular vesicle proteins for biomarker discovery

“…The exosomes are then collected by fractionation collection. Due to the time consuming process, equipment-dependent variability (Zhang et al, 2020), lack of automation (Zhang & Lyden, 2019a), and low yield (Chiang & Chen, 2019), density gradient ultracentrifugation is now losing its popularity (Bryl et al, 2020).…”

“…Microvesicles, on the other hand, are developed via the outward budding of the cell plasma membrane, containing cytosol fragments at random (Doyle & Wang, 2019). Thus, the diverse constituents of exosomes can effectively carry the relevant information of their cellular origin (Bryl et al, 2020; Kalluri & LeBleu, 2020). Figure 2 shows the schematic representation of an exosome.…”

Exosomes Engineering and Their Roles as Therapy Delivery Tools, Therapeutic Targets, and Biomarkers

“…Due to the aforementioned properties, exosomes obtained from various sources and modified by different processes or synthetically produced can be used for a variety of biomedical applications (Figure 11) [15]. They can be used in drug delivery, gene therapy, vaccine development, tissue regeneration, and as biomarkers in the diagnosis and therapy of various diseases, such as cardiovascular diseases, cancer, neurodegenerative diseases, skin regeneration, arthritis, diabetes, and for immunological purposes [15,21,[127][128][129].…”

Mesenchymal Stem Cell-Derived Exosomes and MicroRNAs in Cartilage Regeneration: Biogenesis, Efficacy, miRNA Enrichment and Delivery

“…As this early endosome buds inward, it matures into a late endosome that subsequently undergoes a secondary endosomal membrane invagination to form a multivesicular body containing intraluminal vesicles [80,[83][84][85][86]. These intraluminal vesicles have similar membrane positioning to the cell surface, where extracellular domains of transmembrane protein face the extracellular environment while enclosing the cytosolic entities [87]. As the multivesicular body moves to the cell surface and fuses with it, the intraluminal vesicles are released into the extracellular space, giving rise to exosomes [77].…”

“…As the multivesicular body moves to the cell surface and fuses with it, the intraluminal vesicles are released into the extracellular space, giving rise to exosomes [77]. Other than ESCRT proteins, numerous other accessory proteins have been shown to be involved in the production of exosomes through the ESCRT-dependent pathway, including programmed cell death 6-interacting protein (ALIX); tumor susceptibility gene 101 protein (TSG101); heat shock cognate protein 70 (HSC70); vacuolar protein sorting-associated protein 4 (VPS4); heat shock protein 90 (HSP90); soluble N-ethylmaleimide-sensitive fusion attachment protein receptor (SNAREs); cluster of differentiation proteins 9, 81 and 63; and syndecan-1, synthenin-1, and tetraspanins [79,85,87,88]. In the alternative ESCRTindependent pathway, ceramides play an important role as their cone-shaped feature is speculated to promote microdomain-induced budding of the endosomal membrane.…”