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

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

dc.contributor.author	Mas Bargues, Cristina
dc.contributor.author	Sanz Ros, Jorge
dc.contributor.author	Román Domínguez, Aurora
dc.contributor.author	Gimeno Mallench, Lucia
dc.contributor.author	Inglés de la Torre, Marta
dc.contributor.author	Viña Ribes, José
dc.contributor.author	Borrás, Consuelo
dc.date.accessioned	2020-11-24T09:57:05Z
dc.date.available	2020-11-24T09:57:05Z
dc.date.issued	2020
dc.identifier.citation	Mas Bargues, Cristina Sanz Ros, Jorge Román Domínguez, Aurora Gimeno Mallench, Lucia Inglés de la Torre, Marta Viña Ribes, José Borrás, Consuelo 2020 Extracellular Vesicles from Healthy Cells Improves Cell Function and Stemness in Premature Senescent Stem Cells by miR-302b and HIF-1α Activation. Biomolecules Jun 25 10(6) 957
dc.identifier.uri	https://hdl.handle.net/10550/76453
dc.description.abstract	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.
dc.language.iso	eng
dc.relation.ispartof	Biomolecules, 2020, vol. Jun 25, num. 10(6), p. 957
dc.subject	Fisiologia humana
dc.title	Extracellular Vesicles from Healthy Cells Improves Cell Function and Stemness in Premature Senescent Stem Cells by miR-302b and HIF-1α Activation.
dc.type	journal article	es_ES
dc.date.updated	2020-11-24T09:57:06Z
dc.identifier.doi	10.3390/biom10060957
dc.identifier.idgrec	141368
dc.rights.accessRights	open access	es_ES