Resveratrol Exerts Dosage-Dependent Effects on the Self-Renewal and Neural Differentiation of hUC-MSCs.
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 μM, 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 μM 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 μM of RES. Furthermore, RES could promote neural differentiation in a dose-dependent manner as evidenced by morphological changes and expression of neural markers (Nestin, βIII-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 hUC-MSCs-based therapies for some intractable neurological disorders.
The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China.
Xinxin
X
Wang
School of Life Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province, China.
Shanshan
S
Ma
The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China.
Nan
N
Meng
School of Life Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province, China.
Ning
N
Yao
School of Life Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province, China.
Kun
K
Zhang
School of Life Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province, China.
Qinghua
Q
Li
School of Life Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province, China.
Yanting
Y
Zhang
School of Life Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province, China.
Qu
Q
Xing
School of Life Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province, China.
Kang
K
Han
School of Life Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province, China.
Jishi
J
Song
The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China.
Bo
B
Yang
The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China.|School of Life Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province, China.
Fangxia
F
Guan
D002454:Cell Differentiation / Q000187:drug effects; D000066673:Cell Self Renewal / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects*; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects; D056564:Sirtuin 1 / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology*; D014470:Umbilical Cord / Q000166:cytology*
D018809:Proliferating Cell Nuclear Antigen; D013267:Stilbenes; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D000077185:Resveratrol
SIRT1; human umbilical cord derived mesenchymal stem cells; neural differentiation; resveratrol; self-renewal