Extracellular vesicles and their cells of origin: Open issues in autoimmune diseases

Abstract

The conventional therapeutic approaches to treat autoimmune diseases through suppressing the immune system, such as steroidal and non-steroidal anti-inflammatory drugs, are not adequately practical. Moreover, these regimens are associated with considerable complications. Designing tolerogenic therapeutic strategies based on stem cells, immune cells, and their extracellular vesicles (EVs) seems to open a promising path to managing autoimmune diseases’ vast burden. Mesenchymal stem/stromal cells (MSCs), dendritic cells, and regulatory T cells (Tregs) are the main cell types applied to restore a tolerogenic immune status; MSCs play a more beneficial role due to their amenable properties and extensive cross-talks with different immune cells. With existing concerns about the employment of cells, new cell-free therapeutic paradigms, such as EV-based therapies, are gaining attention in this field. Additionally, EVs’ unique properties have made them to be known as smart immunomodulators and are considered as a potential substitute for cell therapy. This review provides an overview of the advantages and disadvantages of cell-based and EV-based methods for treating autoimmune diseases. The study also presents an outlook on the future of EVs to be implemented in clinics for autoimmune patients.

Cell Type-Specific Extracellular Vesicles and Their Impact on Health and Disease

“…CTS-EVs have become a focal point in the scientific exploration of autoimmune conditions. Generally, immunosuppression is the pathway followed to treat many autoimmune diseases (ADs), though, after some time, the complexity of the human immune system counters its efforts [ 172 ]. Many of today’s steroidal and non-steroidal therapies have dull results due to their inability to offer highly specific effects.…”

“…Many of today’s steroidal and non-steroidal therapies have dull results due to their inability to offer highly specific effects. EVs, on the other hand, have highly configurable packages and can deliver in a targeted fashion [ 172 , 173 ].…”

“…In Sjogren’s syndrome, a disorder affecting the exocrine glands, the scrutiny of CTS-EVs as diagnostic and therapeutic entities is anchored in their distinct molecular composition [ 172 , 181 ]. Originating from salivary and lacrimal gland cells, these EVs encapsulate hallmark biomarkers, including anti-Ro (SSA) and anti-La (SSB) antibodies, indicative of autoimmune responses [ 181 ].…”

Proteomic Profiling of Mesenchymal Stem Cell-Derived Extracellular Vesicles: Impact of Isolation Methods on Protein Cargo

“…EVs have been shown to be involved in various physiological and pathological processes, such as immune response, cancer progression, and neurodegeneration (Beretta et al, 2020; Gupta et al, 2022; Gurung, Perocheau, Touramanidou, & Baruteau, 2021; M. Park et al, 2021; Ruan et al, 2021). These lipid-bound particles have also emerged as promising candidates for therapeutics due to their unique properties, such as biocompatibility, low immunogenicity, and the ability to cross biological barriers (Abyadeh et al, 2023; Barile et al, 2014; Haghighitalab et al, 2023). They can also target specific cells and tissues, making them an attractive alternative to liposomes (Herrmann, Wood, & Fuhrmann, 2021; Mehryab et al, 2020).…”

Dysregulation of extracellular vesicle protein cargo in female myalgic encephalomyelitis/chronic fatigue syndrome cases and sedentary controls in response to maximal exercise

“…EVs are spherical entities protected by a lipid bilayer that range from 30 to 1000 nm in diameter and are detected in most body fluids including blood, urine and saliva. EVs are secreted by skeletal muscle, endothelial, cardiac, hepatic and adipose tissues as well as immune cells, especially platelets (Doyle & Wang, 2019 ; Haghighitalab et al., 2023 ; Kehrloesser et al., 2023 ). The cargo of EVs released after exercise reflects the cellular response to exercise‐induced stress including alterations in metabolism, inflammation, and tissue repair (Whitham et al., 2018 ).…”