Role of p16INK4a and BMI-1 in oxidative stress-induced premature senescence in human dental pulp stem cells

oleh: Cristina Mas-Bargues, José Viña-Almunia, Marta Inglés, Jorge Sanz-Ros, Juan Gambini, José Santiago Ibáñez-Cabellos, José Luis García-Giménez, José Viña, Consuelo Borrás

Format: Article
Diterbitkan: Elsevier 2017-08-01

Deskripsi

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. Keywords: Oxygen tension, Regenerative medicine, Aging