Abstract
Mesenchymal stromal cells (MSCs) are perivascular multipotent stem cells originally identified in the bone marrow (BM) stroma and subsequently in virtually all vascularized tissues. Because of their ability to differentiate into various mesodermal lineages, their trophic properties, homing capacity, and immunomodulatory functions, MSCs have emerged as attractive candidates in tissue repair and treatment of autoimmune disorders. Accumulating evidence suggests that the beneficial effects of MSCs may be primarily mediated via a number of paracrine-acting soluble factors and extracellular vesicles (EVs). EVs are membrane-coated vesicles that are increasingly being acknowledged as playing a key role in intercellular communication via their capacity to carry and deliver their cargo, consisting of proteins, nucleic acids, and lipids to recipient cells. MSC-EVs recapitulate the functions of the cells they originate, including immunoregulatory effects but do not seem to be associated with the limitations and concerns of cell-based therapies, thereby emerging as an appealing alternative therapeutic option in immune-mediated disorders. In the present review, the biology of MSCs will be outlined and an overview of their immunomodulatory functions will be provided. In addition, current knowledge on the features of MSC-EVs and their immunoregulatory potential will be summarized. Finally, therapeutic applications of MSCs and MSC-EVs in autoimmune disorders will be discussed.
Highlights
Knowledge regarding the etiology, pathophysiology, and clinical manifestations of autoimmune disorders has witnessed considerable progress during the last years and this has paved the way for the development of sophisticated treatments targeting molecular pathways and immune deregulations implicated in disease pathogenesis
Using a Theiler’s murine encephalomyelitis virus (TMEV)-induced demyelinating disease as a model of progressive multiple sclerosis (MS), Laso-García et al [179] reported that administration of extracellular vesicles (EVs) derived from adipose tissue-Mesenchymal stromal cells (MSCs) improved motor status, brain atrophy, proliferation in the subventricular zone cells, and decreased inflammatory infiltrates in the mice spinal cord of mice
MSC-based therapies hold great promise for the treatment of immunemediated diseases, variability regarding the origin of MSCs, the age and sex of the donor, isolation and expansion protocols, cell dose, mode, and schedule of administration have resulted in inconsistent results, thereby hindering translation into daily practice
Summary
Pathophysiology, and clinical manifestations of autoimmune disorders has witnessed considerable progress during the last years and this has paved the way for the development of sophisticated treatments targeting molecular pathways and immune deregulations implicated in disease pathogenesis. One such novel therapeutic modality involves the use of mesenchymal stromal sells (MSCs) [1]. Therapeutic applications of MSCs and MSC-EVs in autoimmune disorders will be discussed
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