Mesenchymal Stem Cell-Derived Exosomes: A Promising Therapeutic Ace Card to Address Autoimmune Diseases

Abstract

With the development of novel treatments for autoimmune disorders, it has become a popular research focus which mesenchymal stem cells (MSCs) have the capacity to counteract with autoimmune diseases progression. One of the underlying mechanisms behind their activities is the release of extracellular vesicles especially exosomes. MSC-derived exosomes are hypoimmunogenic nanocarriers which contain numerous immunoregulatory factors and similar to other exosomes, are able to pass through boundaries like the blood-brain barrier (BBB). Accumulating evidence provided by animal studies has demonstrated that MSC-derived exosomes, as a novel therapy, can re-induce self-tolerance, without subsequent complications reported for other treatments. Therefore, therapeutic applications of MSC-derived exosomes are contributing to core advances in the field of autoimmune diseases. Here, we briefly describe the biological characteristics of MSC-derived exosomes and review the experimentally verified outcomes for autoimmune disease therapy purposes.

Extracellular Vesicles as Signaling Mediators and Disease Biomarkers across Biological Barriers

“…MSC-derived exosomes are able to cross the BBB, and many evidence demonstrated that MSC-derived exosomes can re-induce self-tolerance, lowering the subsequent complications with respect to other treatments. Therefore, therapeutic applications of MSC-derived exosomes are contributing to core advances in the field of autoimmune diseases [226].…”

The Role and Impact of Extracellular Vesicles in the Modulation and Delivery of Cytokines during Autoimmunity

“…MSC-derived exosomes have been shown to delay the onset of T1D and experimental autoimmune uveoretinitis by suppressing the activation and development of Th1 and Th17 cells [ 148 ]. Similarly, the administration of MSC-derived exosomes in a model of collagen-induced arthritis was shown to inhibit T-cell proliferation in a dose-dependent manner and reduce the percentage of mature B- and T-cell subsets by inducing TGF-β and IL-10 production in target cells [ 149 ]. In essence, it is possible to engineer EVs with a range of anti-inflammatory cargoes, by either overexpressing cargo in source cells or by loading EVs with synthetic drugs or molecules [ 150 ].…”

From Cancer to Immune-Mediated Diseases and Tolerance Induction: Lessons Learned From Immune Oncology and Classical Anti-cancer Treatment

“…Despite advances in the research and development of novel treatments and biological agents, successful treatment of autoimmune diseases remains unattainable. Recently, both the therapeutic benefit of MSCs and their capacity to counteract autoimmune disease progression was reported ( 106 , 107 ). The immune-modulating effects of MSCs on other lymphoid and myeloid cell types is mediated by the multiple release of mediators, including transforming growth factor beta (TGF-β), prostaglandin E 2 (PGE 2 ), nitric oxide (NO), soluble HLA-G or indoleamine 2, 3-dioxygenase (IDO).…”

“…The immune-modulating effects of MSCs on other lymphoid and myeloid cell types is mediated by the multiple release of mediators, including transforming growth factor beta (TGF-β), prostaglandin E 2 (PGE 2 ), nitric oxide (NO), soluble HLA-G or indoleamine 2, 3-dioxygenase (IDO). Such effects also occur in the presence of increased plasma levels of tumor necrosis factor alpha (TNFa), toll-like receptor 3 (TLR3) agonists and IFNg ( 107 , 108 ). As a result CD4+CD25+CD127– and CD4+CD25+Foxp3+ regulatory T cell (Tregs) subsets are stimulated, resulting in enhanced immunosuppression of cytotoxic CD8+ T cells and CD56 dim CD16+ NK cells ( 107 – 110 ).…”

“…Such effects also occur in the presence of increased plasma levels of tumor necrosis factor alpha (TNFa), toll-like receptor 3 (TLR3) agonists and IFNg ( 107 , 108 ). As a result CD4+CD25+CD127– and CD4+CD25+Foxp3+ regulatory T cell (Tregs) subsets are stimulated, resulting in enhanced immunosuppression of cytotoxic CD8+ T cells and CD56 dim CD16+ NK cells ( 107 – 110 ).…”