Downregulation of APE1/Ref-1 Is Involved in the Senescence of Mesenchymal Stem Cells

摘要: The senescence of human mesenchymal stem cells (hMSCs) causes disruption tissue and organ maintenance, is thus an obstacle to cell-based therapies for disease. Although some researchers have studied changes in the characteristics hMSCs (decreases differentiation ability self-renewal), comparing young old ages, mechanisms cell not yet been defined. In this study, we developed a growth curve bone marrow derived MSCs (hBMSCs) which into hyperbolic state after passage number 7. Senescence associated beta-galactosidase (SA beta-gal) staining hBMSCs showed 10% 9 45% 11. We detected increase endogenous superoxide levels during that correlated with markers beta-gal, curve). Interestingly, even though increased replicative model, expression APE1/Ref-1, sensitive intracellular redox state, decreased. These effects were confirmed stress-induced model by exogenous treatment H(2)O(2). This change related p53 activity negatively regulates APE1/Ref-1. p21 levels, represent activity, transiently 9, meaning they Overexpression APE1/Ref-1 suppressed production decreased SA beta-gal hBMSCs. conclusion, accumulation appears be main cause hBMSCs, overexpression can rescue from phenotype. Maintaining regulating reactive oxygen species contribute regeneration improved therapy.