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13 December 2018

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Int J Med Sci 2014; 11(11):1201-1207. doi:10.7150/ijms.8356

Short Research Communication

Oxidative Stress-Induced Premature Senescence in Wharton's Jelly-Derived Mesenchymal Stem Cells

Kong Bung Choo1,2✉, Lihui Tai1, K.Shri Hymavathee1, Chee Yin Wong3, Phan Nguyen Nhi Nguyen1, Chiu-Jung Huang4, Soon Keng Cheong1,5, Tunku Kamarul6

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;
3. Cytopeutics Sdn Bhd, Selangor, Malaysia;
4. Department of Animal Science & Graduate Institute of Biotechnology, Chinese Culture University, Taipei, Taiwan;
5. Dean's Office, Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Selangor, Malaysia;
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.


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. Conclusion: 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.

Keywords: mesenchymal stem cell, senescence, oxidative stress, hydrogen peroxide.

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How to cite this article:
Choo KB, Tai L, Hymavathee KS, Wong CY, Nguyen PNN, Huang CJ, Cheong SK, Kamarul T. Oxidative Stress-Induced Premature Senescence in Wharton's Jelly-Derived Mesenchymal Stem Cells. Int J Med Sci 2014; 11(11):1201-1207. doi:10.7150/ijms.8356. Available from