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Open AccessArticle

Extracellular Vesicles from Healthy Cells Improves Cell Function and Stemness in Premature Senescent Stem Cells by miR-302b and HIF-1α Activation

1
Freshage Research Group, Department of Physiology, Faculty of Medicine, University of Valencia, CIBERFES-ISCIII, INCLIVA, 46010 Valencia, Spain
2
Freshage Research Group, Department Physiotherapy, Faculty of Physiotherapy, University of Valencia, CIBERFES-ISCIII, INCLIVA, 46010 Valencia, Spain
*
Author to whom correspondence should be addressed.
Biomolecules 2020, 10(6), 957; https://doi.org/10.3390/biom10060957
Received: 25 May 2020 / Revised: 21 June 2020 / Accepted: 22 June 2020 / Published: 25 June 2020
Aging is accompanied by the accumulation of senescent cells that alter intercellular communication, thereby impairing tissue homeostasis and reducing organ regenerative potential. Recently, the administration of mesenchymal stem cells (MSC)-derived extracellular vesicles has proven to be more effective and less challenging than current stem cell-based therapies. Extracellular vesicles (EVs) contain a cell-specific cargo of proteins, lipids and nucleic acids that are released and taken up by probably all cell types, thereby inducing functional changes via the horizontal transfer of their cargo. Here, we describe the beneficial properties of extracellular vesicles derived from non-senescent MSC, cultured in a low physiological oxygen tension (3%) microenvironment into prematurely senescent MSC, cultured in a hyperoxic ambient (usual oxygen culture conditions, i.e., 21%). We observed that senescent MCS, treated with EVs from non-senescent MCS, showed reduced SA-β-galactosidase activity levels and pluripotency factor (OCT4, SOX2, KLF4 and cMYC, or OSKM) overexpression and increased glycolysis, as well as reduced oxidative phosphorylation (OXPHOS). Moreover, these EVs’ cargo induced the upregulation of miR-302b and HIF-1α levels in the target cells. We propose that miR-302b triggered HIF-1α upregulation, which in turn activated different pathways to delay premature senescence, improve stemness and switch energetic metabolism towards glycolysis. Taken together, we suggest that EVs could be a powerful tool to restore altered intercellular communication and improve stem cell function and stemness, thus delaying stem cell exhaustion in aging. View Full-Text
Keywords: oxygen; redox; physioxia; physiological oxygen concentration; extracellular vesicles; aging; senescence oxygen; redox; physioxia; physiological oxygen concentration; extracellular vesicles; aging; senescence
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MDPI and ACS Style

Mas-Bargues, C.; Sanz-Ros, J.; Román-Domínguez, A.; Gimeno-Mallench, L.; Inglés, M.; Viña, J.; Borrás, C. Extracellular Vesicles from Healthy Cells Improves Cell Function and Stemness in Premature Senescent Stem Cells by miR-302b and HIF-1α Activation. Biomolecules 2020, 10, 957.

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