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Abstract
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 (DNMT1, SIRT1), miRNAs (miR-145, miR-148, and miR-185) related to stemness, exosomes, the cell-cycle regulators p21 (WAF1/CIP1) and p53, and the senescence-associated genes (p16, p19, and hTERT). 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 SIRT1 and reduced levels of p21 mRNA. Moreover, we observed a downregulation of DNMT1, and a simultaneous overexpression of Oct-4 and c-Myc. 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.
Highlights
Human mesenchymal stem cells are multipotent elements, capable of restoring tissue function after injuries [1]
We evaluated the expression of stemness-related genes NANOG, Oct-4, SOX2, and c-Myc, and epigenetic modulator genes DNA (cytosine-5)-methyltransferase 1 (DNMT1), SIRT1, and GAPDH
We performed a comparison between the expression levels of these genes in Wharton jelly mesenchymal stem cells (WJ-MSCs) exposed to HepG2-exhausted medium and untreated
Summary
Human mesenchymal stem (or stromal) cells are multipotent elements, capable of restoring tissue function after injuries [1]. Stem cells from Wharton jelly (WJ-MSCs) represent a valuable model of these multipotent cells, and can be obtained without ethical issues [2,3]. While the influence of specific molecules or conditioned media (secretome) on MSCs cultured in vitro and in animal models is largely, how these cells might react to the paracrine effect of cancer cells in vivo is still unclear [9]. C-Myc, and Oct are the main genes involved in cell reprogramming [10,11]. These factors are used for iPSC generation [12,13]. Several studies have shown that reprogramming factors are closely related to various human cancers, including breast cancer, colorectal cancer, and liver cancer [14,15,16,17]
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