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

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Title:	Oxidative Stress-Induced Premature Senescence in Wharton's Jelly-Derived Mesenchymal Stem Cells
Authors:	Choo, Kong Bung Tai, Lihui Hymavathee, K.Shri Wong, Chee Yin Huang, Chiu-Jung Cheong, Soon Keng Kamarul, Tunku
Contributors:	動物科學系
Keywords:	mesenchymal stem cell senescence oxidative stress hydrogen peroxide
Date:	2014
Issue Date:	2015-01-27 14:56:49 (UTC+8)
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 mu M 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-beta-galactosidase, a senescence marker, and were shown to express elevated levels of other well-characterized senescence molecular markers, including p53, p21, p16 and lysosomal beta-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.
Relation:	INTERNATIONAL JOURNAL OF MEDICAL SCIENCES 卷: 11 期: 11 頁碼: 1201-1207
Appears in Collections:	[Department of Animal Science] journal articles

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