3 research outputs found
Small Extracellular Vesicles Have GST Activity and Ameliorate Senescence-Related Tissue Damage
[Abstract]
Aging is a process of cellular and tissue dysfunction characterized by different hallmarks, including cellular senescence. However, there is proof that certain features of aging and senescence can be ameliorated. Here, we provide evidence that small extracellular vesicles (sEVs) isolated from primary fibroblasts of young human donors ameliorate certain biomarkers of senescence in cells derived from old and Hutchinson-Gilford progeria syndrome donors. Importantly, sEVs from young cells ameliorate senescence in a variety of tissues in old mice. Mechanistically, we identified sEVs to have intrinsic glutathione-S-transferase activity partially due to the high levels of expression of the glutathione-related protein (GSTM2). Transfection of recombinant GSTM2 into sEVs derived from old fibroblasts restores their antioxidant capacity. sEVs increase the levels of reduced glutathione and decrease oxidative stress and lipid peroxidation both in vivo and in vitro. Altogether, our data provide an indication of the potential of sEVs as regenerative therapy in aging
Influence of Mesenchymal Stem Cell-Derived Extracellular Vesicles in Vitro and their Role in Ageing
[Abstract]
Introduction: This study assessed whether mesenchymal stem cell (MSC)-derived extracellular vesicles influenced
ageing and pluripotency markers in cell cultures where they are added.
Methods: MSC-derived extracellular vesicles from old and young rat bone marrows were isolated by
ultracentrifugation and were characterised by western blotting, nanoparticle tracking analysis (NTA) and
transmission electron microscopy (TEM). They were added to young and old MSC cultures. Real-time quantitative
reverse transcription polymerase chain reactions and western blot analysis were performed to check the markers of
ageing (vinculin and lamin A), pluripotency markers (Nanog and Oct4) and components of the mTOR signalling
pathway (Rictor, Raptor, AKT and mTOR) in these cell populations. Subsequently, microRNA (miR)-188-3p expression
was transiently inhibited in young MSCs to demonstrate the influence of mTOR2 on MSC ageing.
Results: Incubation with young MSC-derived extracellular vesicles decreased the levels of ageing markers and
components of the mTOR pathway and increased the pluripotency markers from old MSC populations. By contrast,
incubation of young MSCs with old MSC-derived extracellular vesicles generated the reverse effects. Inhibition of
miR-188-3p expression in young MSCs produced extracellular vesicles that when incubated with old MSCs
produced an increase in the levels of Rictor, as well as a decrease of phosphor-AKT, as indicated by a significant
decrease in beta-galactosidase staining.
Conclusions: MSC-derived extracellular vesicles affected the behaviour of MSC cultures, based on their
composition, which could be modified in vitro. These experiments represented the basis for the development of
new therapies against ageing-associated diseases using MSC-derived extracellular vesicles.JAF-L is the recipient of a postdoctoral fellowship funded by ConsellerÃa de Cultura, Educación e Ordenación Universitaria, Xunta de Galicia (Spain