Triggered gta wasted11/27/2023 ![]() The consequences of these stressed EVs in the surrounding microenvironment are not known. It has been described that this “waste-EVs” cargo includes mitochondrial DNA (mtDNA) suggesting that aberrant mitochondrial components may be removed via a vesicular route. Therefore, EV secretion represents a defense mechanism to maintain cellular homeostasis by the excretion of all the intercellular damaged molecules and toxic substances into the extracellular space. ĮVs have long been considered a potential route for cellular waste disposal and it has been proposed that EVs may serve as a reserve mechanism to meet demand when excessive waste production overcomes lysosomal clearance capacity, particularly during oxidative stress. Thus, oxidative stress-related EVs exert both beneficial and harmful effects, as they can carry antioxidants or ROS-generating enzymes and oxidized molecules. On the other hand, the cargo of EVs released under oxidative stress also includes antioxidant molecules that modulate the oxidative stress response in target cells, protecting them against further injury. On the one hand, EVs can convey oxidized lipids and proteins, and this cargo can be responsible for EV-mediated detrimental effects on target cells. Indeed, oxidative stress conditions influence EVs’ release and content, which in turn might modulate the redox status of the receiving cells. It has been suggested that EV biogenesis, shedding, and uptake are redox-sensitive. Moreover, ROS play an important role in the release of mitochondrial cytochrome c and other pro-apoptotic proteins, which can trigger caspase activation and apoptosis. In these conditions, stem cells suffer from oxidative stress as demonstrated by increased reactive oxygen species (ROS) production leading to oxidative damage to proteins and lipids, which ultimately promotes senescence, , ]. These stem cells, when cultivated in vitro, are often subjected to ambient oxygen tension (21%) which represents a much higher oxygen tension. In particular, stem cells reside in niches within the tissues, where the normal oxygen concentration ranges between 3% O 2 and 6% O 2 depending on the vascularization of the tissue. The exact cargo may vary depending on the cell of origin and its specific microenvironment. EVs are small, rounded particles of 50–300 nm, that contain a specific combination of bioactive molecules, such as nucleic acids, proteins, and lipids. This suggests that extracellular vesicles can modulate the cells' microenvironment and the balance between proliferation and senescence.Ĭells communicate with each other among others through extracellular vesicles (EVs). In conclusion, extracellular vesicles from senescent stem cells trigger an adaptive response in young stem cells which improves their antioxidant defenses and their proliferation, migration, and survival rates. This is accompanied by improved cell proliferation, viability, and migration rates and a reduction of apoptosis. The results show that extracellular vesicles from senescent stem cells induce overexpression of antioxidant genes (MnSOD, CAT, and GPx) in young stem cells, which show an increased non-mitochondrial oxygen consumption, accompanied by reduced maximal respiration and spare respiratory capacity without altering mitochondrial membrane potential. Cells were analyzed for antioxidant gene expression, mitochondrial bioenergetic parameters, ROS production, culture kinetics, and apoptosis. Extracellular vesicles were isolated by ultracentrifugation from senescent stem cells and prepared for the treatment of young stem cells at a final concentration of 10 μg/mL. ![]() In this study, we aimed to assess the effect of extracellular vesicles from human dental pulp stem cells cultured under 21% O 2 (senescent stem cells) on human dental pulp stem cells cultured under 3% O 2 (young stem cells). Indeed, oxidative stress conditions influence extracellular vesicles’ release and content, which can modulate the redox status of the receiving cells. Extracellular vesicles' biogenesis, shedding, and uptake are redox-sensitive.
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