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SIRT1 is required for long-term growth of human mesenchymal stem cells

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Abstract

Human mesenchymal stem cells (MSCs) have therapeutic potential because of their ability to self-renew and differentiate into multiple tissues. However, senescence often occurs in MSCs when they are cultured in vitro and the molecular mechanisms underlying this effect remain unclear. In this study, we found that NAD-dependent protein deacetylase SIRT1 is differentially expressed in both human bone marrow-derived MSCs (B-MSCs) and adipose tissue-derived MSCs after increasing passages of cell culture. Using lentiviral shRNA we demonstrated that selective knockdown of SIRT1 in human MSCs at early passage slows down cell growth and accelerates cellular senescence. Conversely, overexpression of SIRT1 delays senescence in B-MSCs that have undergone prolonged in vitro culturing and the cells do not lose adipogenic and osteogenic potential. In addition, we found that the delayed accumulation of the protein p16 is involved in the effect of SIRT1. However, resveratrol, which has been used as an activator of SIRT1 deacetylase activity, only transiently promotes proliferation of B-MSCs. Our findings will help us understand the role of SIRT1 in the aging of normal diploid cells and may contribute to the prevention of human MSCs senescence thus benefiting MSCs-based tissue engineering and therapies.

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Acknowledgments

This work was supported by the National Foundation of Nature Science of China (NO: 31000610), the Major State Basic Research Program of China (No:2011CB64804), and the National High Technology Research and Development Program of China (No:2006AA02A107).

Author disclosure statement

The authors declare that they have no competing financial interests or others that might perceive to influence the results and discussion reported in this paper.

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Authors and Affiliations

  1. Stem Cell and Regeneration Medicine Lab, Beijing Institute of Transfusion Medicine, 27, Taiping Road, Beijing, 100850, China

    Hong-Feng Yuan, Chao Zhai, Xin-Long Yan, Jing-Xue Wang, Quan Zeng, Lin Chen, Xue Nan, Li-Juan He, Si-Ting Li, Wen Yue & Xue-Tao Pei

  2. Department of Hematology, The First Affiliated Hospital of PLA General Hospital, 51, Fucheng Road, Beijing, China, 100037

    Dan-Dan Zhao

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  1. Hong-Feng Yuan
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  2. Chao Zhai
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  11. Wen Yue
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Correspondence to Wen Yue or Xue-Tao Pei.

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Hong-Feng Yuan and Chao Zhai have the same contribution to this work.

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Yuan, HF., Zhai, C., Yan, XL. et al. SIRT1 is required for long-term growth of human mesenchymal stem cells. J Mol Med 90, 389–400 (2012). https://doi.org/10.1007/s00109-011-0825-4

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  • DOI: https://doi.org/10.1007/s00109-011-0825-4

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