RESUMO
Autoimmune diseases are complex, chronic inflammatory conditions initiated by the loss of immunological tolerance to self-antigens. Nowadays, there is no effective and useful therapy for autoimmune diseases, and the existing medications have some limitations due to their nonspecific targets and side effects. During the last few decades, it has been established that mesenchymal stem cells (MSCs) have immunomodulatory functions. It is proposed that MSCs can exert an important therapeutic effect on autoimmune disorders. In parallel with these findings, several investigations have shown that MSCs alleviate autoimmune diseases. Intriguingly, the results of studies have demonstrated that the effective roles of MSCs in autoimmune diseases do not depend on direct intercellular communication but on their ability to release a wide spectrum of paracrine mediators such as growth factors, cytokines and extracellular vehicles (EVs). EVs that range from 50 to 5,000 nm were produced by almost any cell type, and these nanoparticles participate in homeostasis and intercellular communication via the transfer of a broad range of biomolecules such as modulatory proteins, nucleic acids (DNA and RNA), lipids, cytokines, and metabolites. EVs derived from MSCs display the exact properties of MSCs and can be safer and more beneficial than their parent cells. In this review, we will discuss the features of MSCs and their EVs, EVs biogenesis, and their cargos, and then we will highlight the existing discoveries on the impacts of EVs from MSCs on autoimmune diseases such as multiple sclerosis, arthritis rheumatic, inflammatory bowel disease, Type 1 diabetes mellitus, systemic lupus erythematosus, autoimmune liver diseases, Sjögren syndrome, and osteoarthritis, suggesting a potential alternative for autoimmune conditions therapy.
Assuntos
Doenças Autoimunes , Vesículas Extracelulares , Células-Tronco Mesenquimais , Osteoartrite , Humanos , Vesículas Extracelulares/metabolismo , Doenças Autoimunes/terapia , Doenças Autoimunes/metabolismo , Osteoartrite/metabolismo , Células-Tronco Mesenquimais/metabolismo , Citocinas/metabolismoRESUMO
Aging is a biological process determined through time-related cellular and functional impairments, leading to a decreased standard of living for the organism. Recently, there has been an unprecedented advance in the aging investigation, especially the detection that the rate of senescence is at least somewhat regulated via evolutionarily preserved genetic pathways and biological processes. Hematopoietic stem cells (HSCs) maintain blood generation over the whole lifetime of an organism. The senescence process influences many of the natural features of HSC, leading to a decline in their capabilities, independently of their microenvironment. New studies show that HSCs are sensitive to age-dependent stress and gradually lose their self-renewal and regeneration potential with senescence. MicroRNAs (miRNAs) are short, non-coding RNAs that post-transcriptionally inhibit translation or stimulate target mRNA cleavage of target transcripts via the sequence-particular connection. MiRNAs control various biological pathways and processes, such as senescence. Several miRNAs are differentially expressed in senescence, producing concern about their use as moderators of the senescence process. MiRNAs play an important role in the control of HSCs and can also modulate processes associated with tissue senescence in specific cell types. In this review, we display the contribution of age-dependent alterations, including DNA damage, epigenetic landscape, metabolism, and extrinsic factors, which affect HSCs function during aging. In addition, we investigate the particular miRNAs regulating HSCs senescence and age-associated diseases. Video Abstract.