Interaction between mesenchymal stromal cell‐derived extracellular vesicles and immune cells by distinct protein content

Abstract

Mesenchymal stromal cells (MSCs) can effectively contribute to tissue regeneration inside the inflammatory microenvironment mostly through modulating immune responses. MSC‐derived extracellular vesicles (MSC‐EVs) display immunoregulatory functions similar to parent cells. Interactions between MSC‐EVs and immune cells make them an ideal therapeutic candidate for infectious, inflammatory, and autoimmune diseases. These properties of MSC‐EVs have encouraged researchers to perform extensive studies on multiple factors that mediate MSC‐EVs immunomodulatory effects. Investigation of proteins involved in the complex interplay of MSC‐EVs and immune cells may help us to better understand their functions. Here, we performed a comprehensive proteomic analysis of MSC‐EVs that was previously reported by ExoCarta database. A total of 938 proteins were identified as MSC‐EV proteome using quantitative proteomics techniques. Kyoto Encyclopedia of Genes and Genomes analysis demonstrates that ECM–receptor interaction, focal adhesion, and disease‐specific pathways are enriched in MSC‐EVs. By detail analysis of proteins presence in immune system process, we found that expression of some cytokines, chemokines, and chemokine receptors such as IL10, HGF, LIF, CCL2, VEGFC, and CCL20, which leads to migration of MSC‐EVs to injured sites, suppression of inflammation and promotion of regeneration in inflammatory and autoimmune diseases. Also, some chemoattractant proteins such as CXCL2, CXCL8, CXCL16, DEFA1, HERC5, and IFITM2 were found in MSC‐EV proteome. They may actively recruit immune cells to the proximity of MSC or MSC‐EVs, may result in boosting immune response under specific circumstances, and may have protective role in infectious diseases. In this review, we summarize available information about immunomodulation of MSC‐EVs with particular emphasis on their proteomics analysis.

Post-Translational Protein Deimination Signatures in Serum and Serum-Extracellular Vesicles of Bos taurus Reveal Immune, Anti-Pathogenic, Anti-Viral, Metabolic and Cancer-Related Pathways for Deimination

“…ECM-receptor interactions play both direct and indirect roles in controlling multifaceted cellular activities, such as cell differentiation, migration and proliferation as well as cell adhesion and apoptosis [193]. ECM-receptor interaction KEGG pathways have been identified in cancer [193] and enrichment for this pathway has been reported mesenchymal stem cell EVs [194]. Regulation of ECM-receptor interactions via post-translational deimination has recently been identified by our group via enrichment of deiminated proteins in KEGG pathways for ECM-receptor interactions in the fin whale, a long-lived cancer-resistant animal [96], in the alligator, an animal with unusual antibacterial and anti-viral responses [93], in the wandering albatross (Diomedea exulans), also an unusually long-lived bird for an avian species [99], as well as in aggressive brain cancer cells [100].…”

Oral Mesenchymal Stem/Progenitor Cells: The Immunomodulatory Masters

“…Although EVs in the oral MSC-derived conditioned media play a pivotal role in cell-cell communication, the information exchange between oral MSCs and their surrounding inflammatory microenvironment is bidirectional. EVs liberated from oral MSCs could restrain the inflammatory response in immune cells, and conversely immune cells could affect the proliferation, differentiation, and migration potential of MSCs, through their EVs [113,114]. In an Ec-LPS-challenged inflammatory environment, monocyte-derived exosomes could promote the osteogenic differentiation of BM-MSCs [115].…”

Extracellular vesicles, news about their role in immune cells: physiology, pathology and diseases

“…This role of EVs has been confirmed by in-vitro studies, where the cells employed for their release are often of a single type, and target cells are known. The EVs most effective for intervention in the latter responses are those derived from mesenchymal stromal cells (MSCs) [26]. The EVs from pathogens are relevant for various reasons: on one hand, for the co-ordinated activity of bacteria; on the other hand, for lesions of host cells, including alterations of immune recognition and cellular responses [24][25][26].…”

“…EVs are often important for animals and humans, especially when afflicted by infectious diseases. The EVs from pathogens are relevant for various reasons: on one hand, for the co-ordinated activity of bacteria; on the other hand, for lesions of host cells, including alterations of immune recognition and cellular responses [24][25][26]. The EVs most effective for intervention in the latter responses are those derived from mesenchymal stromal cells (MSCs) [26].…”

“…The EVs from pathogens are relevant for various reasons: on one hand, for the co-ordinated activity of bacteria; on the other hand, for lesions of host cells, including alterations of immune recognition and cellular responses [24][25][26]. The EVs most effective for intervention in the latter responses are those derived from mesenchymal stromal cells (MSCs) [26]. When the investigation of inflammation depends on the analysis of EVs from the blood plasma, the origin of these vesicles includes various types of cells, especially platelets, endothelia and leucocytes.…”