Behavioral Changes in Stem-Cell Potency by HepG2-Exhausted Medium

Cells. 2020 Aug 12;9(8):1890. doi: 10.3390/cells9081890.

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.

Keywords: cellular mechanisms; exosomes; miRNA; stem cell differentiation and proliferation; stem cells; stemness genes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Culture Techniques / methods*
  • Cell Differentiation / genetics
  • Cellular Senescence / genetics
  • Culture Media, Conditioned
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics
  • DNA (Cytosine-5-)-Methyltransferase 1 / genetics
  • Gene Expression Regulation, Neoplastic
  • Hep G2 Cells
  • Humans
  • Mesenchymal Stem Cells / metabolism*
  • MicroRNAs / genetics
  • Octamer Transcription Factor-3 / genetics
  • Phenotype*
  • Proto-Oncogene Proteins c-myc / genetics
  • Sirtuin 1 / genetics
  • Wharton Jelly / cytology*

Substances

  • CDKN1A protein, human
  • Culture Media, Conditioned
  • Cyclin-Dependent Kinase Inhibitor p21
  • MYC protein, human
  • MicroRNAs
  • Octamer Transcription Factor-3
  • POU5F1 protein, human
  • Proto-Oncogene Proteins c-myc
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNMT1 protein, human
  • SIRT1 protein, human
  • Sirtuin 1