MicroRNA-18a prevents senescence of mesenchymal stem cells by targeting CTDSPL.

Stem cell therapy requires massive-scale homogeneous stem cells under strict qualification control. However, Prolonged ex vivo expansion impairs the biological functions and results in senescence of mesenchymal stem cells (MSCs). We investigated the function of CTDSPL in the premature senescence process of MSCs and clarified that miR-18a-5p played a prominent role in preventing senescence of long-term cultured MSCs and promoting the self-renewal ability of MSCs. Over-expression of CTDSPL resulted in an enlarged morphology, up-regulation of p16 and accumulation of SA-ß-gal of MSCs. The reduced phosphorylated RB suggested cell cycle arrest of MSCs. All these results implied that CTDSPL induced premature senescence of MSCs. We further demonstrated that miR-18a-5p was a putative regulator of CTDSPL by luciferase reporter assay. Inhibition of miR-18a-5p promoted the expression of CTDSPL and induced premature senescence of MSCs. Continuous overexpression of miR-18a-5p improved self-renewal of MSCs by reducing ROS level, increased expression of Oct4 and Nanog, and promoted growth rate and differentiation capability. We reported for the first time that the dynamic interaction of miR-18a-5p and CTDSPL is crucial for stem cell senescence.

MiR-218 Induces Neuronal Differentiation of ASCs in a Temporally Sequential Manner with Fibroblast Growth Factor by Regulation of the Wnt Signaling Pathway.

Differentiation of neural lineages from mesenchymal stem cells has raised the hope of generating functional cells as seed cells for nerve tissue engineering. As important gene regulators, microRNAs (miRNAs) have been speculated to play a vital role in accelerating stem cell differentiation and repairing neuron damage. However, miRNA roles in directing differentiation of stem cells in current protocols are underexplored and the mechanisms of miRNAs as regulators of neuronal differentiation remain ambiguous. In this study, we have determined that miR-218 serves as crucial constituent regulator in neuronal differentiation of adipose stem cells (ASCs) through Wnt signaling pathway based on comprehensive annotation of miRNA sequencing data. Moreover, we have also discovered that miR-218 and Fibroblast Growth Factor-2 (FGF2) modulate neuronal differentiation in a sequential manner. These findings provide additional understanding of the mechanisms regulating stem cell neuronal differentiation as well as a new method for neural lineage differentiation of ASCs.

Mechanism study for hypoxia induced differentiation of insulin-producing cells from umbilical cord blood-derived mesenchymal stem cells.

Recently, we have successfully obtained functional IPCs efficiently from umbilical cord blood-derived mesenchymal stem cells by using hypoxia treatment. In this study, we further elaborated that the improved function and viability of IPCs are the result of the interaction ß cell development pathway and c-Met/HGF axis induced by hypoxia. We found that hypoxia induced c-MET elevation is efficiently initiated the early stage differentiation IPCs from MSCs, and HGF improved the fully differentiation of IPCs by inducing the expression of NGN3. This finding may contribute to understanding ß cell development and the development of stem cell therapy for diabetes.

Protective effect of estrogen on apoptosis in a cell culture model of Parkinson's disease.

OBJECTIVES: The protective effect of estrogen on the neurons in Parkinson's disease (PD) is unclear. The present study aimed to investigate the effect of estrogen on the apoptosis and dopaminergic function on a cultured cell model of PD. METHODS: The PD model was established by addition of 1-methyl-4-phenylpyridinium (MPP+) to PC12 cell culture. Estrogen was added to cell groups with MPP+ (Estrogen+MPP+), and without MPP+ (Estrogen only group). Cell viability, content of tyrosine hydroxylase (TH), apoptosis ratio, expression of apoptosis-suppression protein Bcl-x and apoptosis-acceleration protein IL-1 beta converting enzyme (ICE) were measured. RESULTS: Cell viability in the Estrogen+MPP+ group was similar to the control group but was higher than in the MPP+ group (P < 0.05). The apoptosis ratios in the Estrogen+MPP+ group (33.6%), and the control group (31.3%), were also similar, but it was lower than in the MPP+ group (63.5%, P < 0.05). Concentrations of Bcl-x were higher in the Estrogen+MPP+ group, whereas ICE concentrations were lower than in the MPP+ group (P < 0.05). CONCLUSIONS: Estrogen suppresses apoptosis and improves cell viability in MPP+ induced injuries in the PC12 cells. The beneficial effects of estrogen on the PD model are due to the suppression of pro-apoptotic protein ICE, and stimulation of anti-apoptotic protein Bcl-x.