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

Francesca Balzano1, Giuseppe Garroni1, Sara Cruciani1

  • 1Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/B, 07100 Sassari, Italy.

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|August 19, 2020
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Summary
This summary is machine-generated.

Wharton jelly mesenchymal stem cells (WJ-MSCs) maintain stemness when exposed to HepG2-conditioned medium, showing altered gene expression related to pluripotency and cell cycle regulation. This suggests a shift towards proliferation rather than differentiation.

Keywords:
cellular mechanismsexosomesmiRNAstem cell differentiation and proliferationstem cellsstemness genes

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Area of Science:

  • Stem Cell Biology
  • Epigenetics
  • Cellular Senescence

Background:

  • Wharton jelly mesenchymal stem cells (WJ-MSCs) possess differentiation potential crucial for tissue regeneration.
  • Stemness is regulated by a balance of pluripotency and differentiation genes, influenced by epigenetic factors and microRNAs.
  • Cellular microenvironment, including factors secreted by other cell types, can impact stem cell behavior.

Purpose of the Study:

  • To investigate the effects of HepG2 cell-conditioned medium on WJ-MSC stemness, differentiation, and senescence.
  • To analyze the expression of key stemness-related genes, epigenetic regulators, miRNAs, and senescence markers in WJ-MSCs.
  • To understand how the cellular environment influences WJ-MSC phenotype and behavior.

Main Methods:

  • WJ-MSCs were cultured in standard medium versus medium conditioned by the human hepatocarcinoma cell line HepG2.
  • Gene expression analysis was performed for stemness markers (Oct-4, c-Myc), epigenetic regulators (DNMT1, SIRT1), cell cycle regulators (p21, p53), and senescence markers (p16, p19, hTERT).
  • MicroRNA expression (miR-145, miR-148, miR-185) and exosome presence were also assessed.

Main Results:

  • HepG2-conditioned medium led to overexpression of SIRT1 and stemness genes (Oct-4, c-Myc).
  • A significant downregulation of DNMT1 and p21 mRNA levels was observed.
  • WJ-MSCs exhibited characteristics suggesting retained stemness and a potential shift towards a proliferative, undifferentiated state.

Conclusions:

  • HepG2-conditioned medium promotes a stem-like phenotype in WJ-MSCs by modulating epigenetic regulators and cell cycle pathways.
  • WJ-MSCs treated with HepG2-conditioned medium may favor proliferation over differentiation, indicating altered stemness.
  • These findings highlight the influence of the tumor microenvironment on mesenchymal stem cell behavior.