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Resveratrol Exerts Dosage-Dependent Effects on the Self-Renewal and Neural Differentiation of hUC-MSCs

  • Wang, Xinxin (The First Affiliated Hospital of Zhengzhou University) ;
  • Ma, Shanshan (School of Life Sciences, Zhengzhou University) ;
  • Meng, Nan (The First Affiliated Hospital of Zhengzhou University) ;
  • Yao, Ning (School of Life Sciences, Zhengzhou University) ;
  • Zhang, Kun (School of Life Sciences, Zhengzhou University) ;
  • Li, Qinghua (School of Life Sciences, Zhengzhou University) ;
  • Zhang, Yanting (School of Life Sciences, Zhengzhou University) ;
  • Xing, Qu (School of Life Sciences, Zhengzhou University) ;
  • Han, Kang (School of Life Sciences, Zhengzhou University) ;
  • Song, Jishi (School of Life Sciences, Zhengzhou University) ;
  • Yang, Bo (The First Affiliated Hospital of Zhengzhou University) ;
  • Guan, Fangxia (The First Affiliated Hospital of Zhengzhou University)
  • Received : 2015.12.16
  • Accepted : 2016.04.06
  • Published : 2016.05.31

Abstract

Resveratrol (RES) plays a critical role in the fate of cells and longevity of animals via activation of the sirtuins1 (SIRT1) gene. In the present study, we intend to investigate whether RES could promote the self-renewal and neural-lineage differentiation in human umbilical cord derived MSCs (hUC-MSCs) in vitro at concentrations ranging from 0.1 to $10{\mu}M$, and whether it exerts the effects by modulating the SIRT1 signaling. Herein, we demonstrated that RES at the concentrations of 0.1, 1 and $2.5{\mu}M$ could promote cell viability and proliferation, mitigate senescence and induce expression of SIRT1 and Proliferating Cell Nuclear Antigen (PCNA) while inhibit the expression of p53 and p16. However, the effects were reversed by 5 and $10{\mu}M$ of RES. Furthermore, RES could promote neural differentiation in a dose-dependent manner as evidenced by morphological changes and expression of neural markers (Nestin, ${\beta}III-tubulin$ and NSE), as well as pro-neural transcription factors Neurogenin (Ngn)1, Ngn2 and Mash1. Taken together, RES exerts a dosage-dependent effect on the self-renewal and neural differentiation of hUC-MSCs via SIRT1 signaling. The current study provides a new strategy to regulate the fate of hUC-MSCs and suggests a more favorable in vitro cell culture conditions for hUCMSCs-based therapies for some intractable neurological disorders.

Keywords

human umbilical cord derived mesenchymal stem cells;neural differentiation;resveratrol;self-renewal;SIRT1

Acknowledgement

Supported by : National Natural Science Foundation of China

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