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.