| Summary: | Wharton jelly mesenchymal stem cells (WJ-MSCs) are able to differentiate into different cell lineages upon stimulation. This ability is closely related to the perfect balance between the pluripotency-related genes, which control stem-cell proliferation, and genes able to orchestrate the appearance of a specific phenotype. Here we studied the expression of stemness-related genes, epigenetic regulators (<i>DNMT1, SIRT1</i>), miRNAs (<i>miR-145, miR-148</i>, and <i>miR-185</i>) related to stemness, exosomes, the cell-cycle regulators <i>p21</i> (<i>WAF1/CIP1</i>) and <i>p53</i>, and the senescence-associated genes (<i>p16, p19</i>, and <i>hTERT</i><i>)</i>. Cells were cultured in the presence or absence of the human hepatocarcinoma cell line HepG2-exhausted medium, to evaluate changes in stemness, differentiation capability, and senescence sensibility. Our results showed the overexpression of <i>SIRT1</i> and reduced levels of <i>p21</i> mRNA. Moreover, we observed a downregulation of <i>DNMT1</i>, and a simultaneous overexpression of <i>Oct-4</i> and <i>c-Myc</i>. These findings suggest that WJ-MSCs are more likely to retain a stem phenotype and sometimes to switch to a highly undifferentiable proliferative-like behavior if treated with medium exhausted by human HepG2 cell lines.
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