Mesenchymal stromal cell-derived extracellular vesicles: regenerative and immunomodulatory effects and potential applications in sepsis

Abstract

Mesenchymal stromal (stem) cells (MSCs) have multipotent differentiation capacity and exist in nearly all forms of post-natal organs and tissues. The immunosuppressive and anti-inflammatory properties of MSCs have made them an ideal candidate in the treatment of diseases, such as sepsis, in which inflammation plays a critical role. One of the key mechanisms of MSCs appears to derive from their paracrine activity. Recent studies have demonstrated that MSC-derived extracellular vesicles (MSC-EVs) are at least partially responsible for the paracrine effect. MSC-EVs transfer molecules (such as proteins/peptides, mRNA, microRNA and lipids) with immunoregulatory properties to recipient cells. MSC-EVs have been shown to mimic MSCs in alleviating sepsis and may serve as an alternative to whole cell therapy. Compared with MSCs, MSC-EVs may offer specific advantages due to lower immunogenicity and higher safety profile. The first two sections of the review discuss the preclinical and clinical findings of MSCs in sepsis. Next, we review the characteristics of EVs and MSC-EVs. Then, we summarize the mechanisms of MSC-EVs, including tissue regeneration and immunomodulation. Finally, our review presents the evidences that MSC-EVs are effective in treating models of sepsis. In conclusion, MSC-EVs may have the potential to become a novel therapeutic strategy for sepsis.

Local delivery of USC-derived Exosome Carrying ANGPTL3 Enhance Spinal Cord Functional Recovery After Injury by Promoting Angiogenesis

“…In additional, exosome are cell-free treatment and non-immunogenic in nature and, and possess intrinsic ability selectively delivered to target tissues, and has long circulation times in the body, makes them ideal candidates for targeted therapy by effectively transfer of different kinds of molecules upon genetically modifying [30][31][32]. The biological modi cation with pro-regenerative factor may enhance the innate therapeutic capability of exosomes [33].…”

Role of Mesenchymal Stromal Cells as Therapeutic Agents: Potential Mechanisms of Action and Implications in Their Clinical Use

“…Despite the evidence about MSCs direct differentiation and cell replacement, recent studies strongly suggest that the most remarkable MoA of MSCs are attributed to their capacity of migration [17] and paracrine effect [30,31], as well as the modifications that MSCs can cause over the immune system (immunomodulation) [32,33].…”

“…In addition to secreted factors, the paracrine-protective mechanisms of MSCs include the production of EVs, which include exosomes, and transfer of mitochondria [32,78,79]. Recently, it has been shown that the EVs from MSCs contain vesicular cargo molecules that include messenger RNA, transfer RNA, microRNA, and peptides/proteins.…”

“…For example, the treatment of murine alveolar macrophages with MSC-derived EVs reduce lung injury due to MSCs induce a highly phagocytic and antiinflammatory macrophage phenotype through EV-mediated mitochondrial transfer [91]. production of EVs, which include exosomes, and transfer of mitochondria [32,78,79]. Recently, it has been shown that the EVs from MSCs contain vesicular cargo molecules that include messenger RNA, transfer RNA, microRNA, and peptides/proteins.…”

MSC-derived miR-181b Overexpressing Exosomes Enhanced Osteointegration by Enhancing M2 Polarization of Macrophages via Targeting the PRKCD/AKT Pathway

“…Since miRNA is one of the cargos that could be used in tissue regeneration [14]. Thus, we could establish modularized extracellular vesicles by endowing the exosomes with speci c miRNA via overexpression method by transfection [13] MSCs are cells with immunomodulatory and multipotent abilities, which will be bene cial for in ammation-related diseases [15]. It has been reported that exosomes derived from hBMSC could regulate macrophage phenotypes and exert immunomodulatory effect because these two types of cells coexist in bone marrow and there exists cellular communication mediated by extracellular vesicles such as exosomes [16,17].…”