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Role of histone deacetylase inhibitors in the aging of human umbilical cord mesenchymal stem cells

Authors

  • Yunshuai Wang,

    1. Department of General Surgery, The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, Shenzhen, China
    2. Laboratory of Stem Cell and Cellular Therapy, The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, Shenzhen, China
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  • Tao Chen,

    1. Laboratory of Stem Cell and Cellular Therapy, The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, Shenzhen, China
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  • Hongjie Yan,

    1. Laboratory of Stem Cell and Cellular Therapy, The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, Shenzhen, China
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  • Hui Qi,

    1. Laboratory of Stem Cell and Cellular Therapy, The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, Shenzhen, China
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  • Chunyan Deng,

    1. Laboratory of Stem Cell and Cellular Therapy, The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, Shenzhen, China
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  • Tao Ye,

    1. Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong SAR, China
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  • Shuyan Zhou,

    1. Laboratory of Stem Cell and Cellular Therapy, The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, Shenzhen, China
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  • Fu-Rong Li

    Corresponding author
    1. Laboratory of Stem Cell and Cellular Therapy, The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, Shenzhen, China
    • Department of General Surgery, The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, Shenzhen, China
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Correspondence to: Fu-Rong Li, Laboratory of Stem Cell and Cellular therapy, The Second Clinical Medical College (Shenzhen People's Hospital) Ji'nan University, 1017 Dongmen North Road, Shenzhen 518020, China.

E-mail: frli62@yahoo.com

ABSTRACT

Mesenchymal stem cells (MSCs) are self-renewing cells that exhibit differentiation capacity and immune regulation ability. These versatile cells have a wide range of potential applications. However, the spontaneous differentiation and aging of MSCs during long-term culturing restrict the amount of cells available for therapies and tissue engineering. Thus, maintaining the biological characteristics of MSCs during long-term culturing is crucial. Chromatic modification via epigenetic regulatory mechanisms (e.g., histone acetylation, deacetylation, and methylation) is crucial in stem cell pluripotency. We investigated the effects of largazole or trichostatin A (TSA), a novel histone deacetylase inhibitor (HDACi), against human umbilical cord (hUC)-MSCs aging. Results show that low concentrations of largazole or TSA can significantly improve hUC-MSCs proliferation and delay hUC-MSCs aging. Largazole can better improve MSCs proliferation than TSA. HDAC is modulate histone H3 acetylation and methylation in the telomerase reverse-transcriptase, octamer-binding transcription factor 4, Nanog, C-X-C chemokine receptor 4, alkaline phosphatase, and osteopontin genes. HDACis can promote hUC-MSCs proliferation and suppress hUC-MSCs spontaneous osteogenic differentiation. HDACis can affect histone H3 lysine 9 or 14 acetylation and histone H3 lysine 4 dimethylation, thus increasing the mRNA expression of pluripotent and proliferative genes and suppressing the spontaneous differentiation of hUC-MSCs. J. Cell. Biochem. 114: 2231–2239, 2013. © 2013 Wiley Periodicals, Inc.

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