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RESEARCH PRODUCT
Role of p16INK4a and BMI-1 in oxidative stress-induced premature senescence in human dental pulp stem cells
Jose Viña-almuniaJuan GambiniConsuelo BorrasJorge Sanz-rosJose ViñaJosé Santiago Ibáñez-cabellosMarta InglesJosé Luis García-jiménezCristina Mas Barguessubject
AdultMale0301 basic medicineSenescenceAginghDPSCs human dental pulp stem cellsMSC mesenchymal stem cellsAdolescentCellular differentiationClinical BiochemistryCell Culture TechniquesOSKM OCT4 SOX2 KLF4 and c-MYCBiologymedicine.disease_causeBiochemistryCell therapyKruppel-Like Factor 4Young Adult03 medical and health sciencesDental pulp stem cellsmedicineHumansOxygen tensionlcsh:QH301-705.5SIPS stress-induced premature senescenceCells CulturedCellular SenescenceCyclin-Dependent Kinase Inhibitor p16Dental PulpMDA malondialdehydePolycomb Repressive Complex 1lcsh:R5-920Stem CellsOrganic ChemistryCell DifferentiationOxygen tensionCell biologyOxygenOxidative Stress030104 developmental biologylcsh:Biology (General)Cell cultureRegenerative medicineImmunologyFemaleStem celllcsh:Medicine (General)Oxidative stressResearch Paperdescription
Human dental pulp stem cells (hDPSCs) are a source for cell therapy. Before implantation, an in vitro expansion step is necessary, with the inconvenience that hDPSCs undergo senescence following a certain number of passages, loosing their stemness properties. Long-term in vitro culture of hDPSCs at 21% (ambient oxygen tension) compared with 3–6% oxygen tension (physiological oxygen tension) caused an oxidative stress-related premature senescence, as evidenced by increased β-galactosidase activity and increased lysil oxidase expression, which is mediated by p16INK4a pathway. Furthermore, hDPSCs cultured at 21% oxygen tension underwent a downregulation of OCT4, SOX2, KLF4 and c-MYC factors, which was recued by BMI-1 silencing. Thus, p16INK4a and BMI-1 might play a role in the oxidative stress-associated premature senescence. We show that it is important for clinical applications to culture cells at physiological pO2 to retain their stemness characteristics and to delay senescence.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2017-08-01 | Redox Biology |