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Characterization of EVs. (A) Transmission electron microscopy image of MSC-EVs (arrow). Scale bar, 100 nm. (B) Size distribution of MSC-EVs was investigated by nanoparticle tracking analysis (NTA). (C) Western blot analysis of EV-associated markers, Alix, TSG101, and CD9 and negative control, Calnexin. (D) Western blot analysis of MSC-associated markers, CD73, CD90 and CD105
Source publication
Compelling evidence suggests that mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) promote regeneration in animal models of liver injury by delivering signaling molecules. However, their target cells and uptake mechanism remain elusive. In this study, MSC-EVs were intravenously administered in a mouse model of liver ischemia-reperfusi...
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Citations
... Current research indicates that MSC-EVs can aggregate at injury sites, akin to their parental cells, but the precise mechanisms underlying this targeting remain elusive. For instance, MFGE8, a lipophilic glycoprotein enriched in MSC-EVs, has been shown to bind to phosphatidylserine (PS) on injured cells, facilitating the targeting of EVs to damaged tissues and the subsequent release of therapeutic factors [94]. However, the complexity of EV components, including various miRNAs and proteins, suggests that multiple pathways may be involved in their therapeutic effects. ...
Radiation injury is a severe issue in both nuclear accidents and cancer radiotherapy. Ionizing radiation impairs the regenerative and repair capabilities of tissues and organs, resulting in a scarcity of effective therapeutic approaches to prevent or mitigate such injuries. Mesenchymal stem cells (MSCs) possess favorable biological characteristics and have emerged as ideal candidates for the treatment of radiation injury. However, the use of MSCs as therapeutic agents is associated with uncertainties in therapeutic efficacy, transient effects, and the risk of immune rejection. Recent advances in research have revealed that extracellular vesicles (EVs) derived from mesenchymal stem cells (MSC-EVs) exhibit similar beneficial properties to MSCs and represent a promising cell-free therapy for mitigating radiation injuries. MSC-EVs are enriched with microRNAs (miRNAs), proteins, and lipids, which can modulate immune responses, inflammatory reactions, cell survival, and proliferation in irradiated tissues. This review synthesizes recent studies on the application of MSC-EVs in radiation injury, focusing on the therapeutic effects and mechanisms of MSC-EVs derived from various sources in radiation-induced diseases of different organs. The therapeutic potential of MSC-EVs for radiation injury provides valuable insights for addressing ionizing radiation-induced injuries and offers a reference for future clinical applications.
... Recent studies have indicated that the therapeutic potential of MSCs relies mainly on EVs secreted by MSCs [24,25]. Extracellular vesicles (EVs), which are membrane-packed nanovesicles, mediate intercellular communication by transferring cargos (miRNAs, circular RNAs, proteins and lipids) to target cells and are a cell-free therapy alternative, with the advantages of preventing immunogenicity, tumorigenicity, easy storage and production, and passing through biological barriers [3,26,27]. Studies have shown that MSC-EVs can yield beneficial therapeutic effects on DKD [28,29]. However, the underlying mechanisms by which MSC-EVs alleviate DKD remain to be fully elucidated. ...
... EVs were harvested from the supernatant of hP-MSCs as previously described [3,27]. Briefly, EV-free FBS was obtained by centrifugation of FBS at 100,000 × g for 2 h. ...
Background
Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease (ESRD) globally, presenting a significant therapeutic challenge. Extracellular vesicles (EVs) from mesenchymal stem cells (MSCs) have emerged as promising therapeutic agents. This study explored the therapeutic effects and mechanisms of EVs derived from human placental mesenchymal stem cells (hP-MSCs) on DKD.
Methods
EVs were isolated from cultured hP-MSCs and administered to streptozotocin (STZ)-induced diabetic mice and high glucose–treated glomerular mesangial cells. The therapeutic impact of EVs was assessed through histological analysis and biochemical assays. miR-99b-5p expression in EVs and its role in modulating the mechanistic target of rapamycin (mTOR)/autophagy pathway were examined via western blotting and RT‒qPCR.
Results
Treatment with hP-MSC-derived EVs significantly alleviated renal fibrosis and improved renal function in DKD models. These EVs were enriched with miR-99b-5p, which targeted and inhibited mTOR signaling, thereby increasing autophagic activity and reducing cellular proliferation and extracellular matrix accumulation in renal tissues.
Conclusions
hP-MSC-derived EVs can mitigate renal injury in DKD by modulating the miR-99b-5p/mTOR/autophagy pathway. These findings suggest a potential cell-free therapeutic strategy for managing DKD.
