title: Oxidative stress-induced premature senescence in Wharton's jelly-derived mesenchymal stem cells.
abstract: BACKGROUND
  On in vitro expansion for therapeutic purposes, the regenerative potentials of mesenchymal stem cells (MSCs) decline and rapidly enter pre-mature senescence probably involving oxidative stress. To develop strategies to prevent or slow down the decline of regenerative potentials in MSC culture, it is important to first address damages caused by oxidative stress-induced premature senescence (OSIPS). However, most existing OSIPS study models involve either long-term culture to achieve growth arrest or immediate growth arrest post oxidative agent treatment and are unsuitable for post-induction studies.
  
  
  METHODS
  In this work, we aimed to establish an OSIPS model of MSCs derived from Wharton's Jelly by hydrogen peroxide (H2O2) treatment.
  
  
  RESULTS
  The optimal H2O2 concentration was determined to be 200 µM to achieve OSIPS when MSC reached growth arrest in 3 to 4 passages post-H2O2 treatment. H2O2-treated cells became heterogeneous in morphology, and were irregularly enlarged and flattened with granular cytoplasm. The cells were stained positive for SA-β-galactosidase, a senescence marker, and were shown to express elevated levels of other well-characterized senescence molecular markers, including p53, p21, p16 and lysosomal β-galactosidase (GLB1) in real-time RT-PCR analysis. The OSIPS-like features were confirmed with three independent WJ-MSC lines.
  
  
  CONCLUSIONS
  The establishment of an OSIPS model of WJ-MSC is a first step for subsequent investigation on molecular mechanisms of senescence and for screening potential anti-oxidative agents to delay or revert stressed-induced senescence.
authors.affiliation: 1. Centre for Stem Cell Research, Universiti Tunku Abdul Rahman, Selangor, Malaysia; ; 2. Department of Preclinical Sciences, Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Selangor, Malaysia;
authors.forename: Kong Bung
authors.initials: KB
authors.lastname: Choo
authors.affiliation: 1. Centre for Stem Cell Research, Universiti Tunku Abdul Rahman, Selangor, Malaysia;
authors.forename: Lihui
authors.initials: L
authors.lastname: Tai
authors.affiliation: 1. Centre for Stem Cell Research, Universiti Tunku Abdul Rahman, Selangor, Malaysia;
authors.forename: K Shri
authors.initials: KS
authors.lastname: Hymavathee
authors.affiliation: 3. Cytopeutics Sdn Bhd, Selangor, Malaysia;
authors.forename: Chee Yin
authors.initials: CY
authors.lastname: Wong
authors.affiliation: 1. Centre for Stem Cell Research, Universiti Tunku Abdul Rahman, Selangor, Malaysia;
authors.forename: Phan Nguyen Nhi
authors.initials: PN
authors.lastname: Nguyen
authors.affiliation: 4. Department of Animal Science & Graduate Institute of Biotechnology, Chinese Culture University, Taipei, Taiwan;
authors.forename: Chiu-Jung
authors.initials: CJ
authors.lastname: Huang
authors.affiliation: 1. Centre for Stem Cell Research, Universiti Tunku Abdul Rahman, Selangor, Malaysia; ; 5. Dean's Office, Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Selangor, Malaysia;
authors.forename: Soon Keng
authors.initials: SK
authors.lastname: Cheong
authors.affiliation: 6. Tissue Engineering Group, National Orthopaedic Centre of Excellence for Research and Learning, Department of Orthopaedic Surgery, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Tunku
authors.initials: T
authors.lastname: Kamarul
mesh_terms: D002460:Cell Line; D016922:Cellular Senescence / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D060888:Real-Time Polymerase Chain Reaction; D059631:Wharton Jelly / Q000166:cytology*
chemical_list: D006861:Hydrogen Peroxide
keywords: hydrogen peroxide.; mesenchymal stem cell; oxidative stress; senescence