Journal
REDOX BIOLOGY
Volume 12, Issue -, Pages 690-698Publisher
ELSEVIER
DOI: 10.1016/j.redox.2017.04.002
Keywords
Oxygen tension; Regenerative medicine; Aging
Categories
Funding
- Spanish Ministry of Education and Science (MEC) [SAF2010-19498, SAF2013-44663-R, SAF2016-75508-R]
- Red Tematica de investigacion cooperativa en envejecimiento y fragilidad (RETICEF) [ISCIII2006-RED13-027, ISCIII2012-RED-43-029]
- CIBERFES [ISCIII2016-CIBER]
- Valencia International Campus of Excellence (VLC/CAMPUS of the University of Valencia) Conselleria de Educacion, Cultura y Deporte [PROMETEO2010/074, ACIF2014/165]
- European Union [CM1001, FRAILOMIC-HEALTH.2012.2.1.1-2]
- FEDER funds from the European Union
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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 beta-galactosidase activity and increased lysil oxidase expression, which is mediated by p16(INK4a) 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, p16(INK4a) 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 pO(2) to retain their stemness characteristics and to delay senescence.
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