Comparison of Oxidative Stress Effects on Senescence Patterning of Human Adult and Perinatal Tissue-Derived Stem Cells in Short and Long-term Cultures

Abstract

Human Mesenchymal Stem Cells (hMSCs) undergo senescence in lifespan. In most clinical trials, hMSCs experience long-term expansion <i>ex vivo</i> to increase cell number prior to transplantation, which unfortunately leads to cell senescence, hampering post-transplant outcomes. Hydrogen peroxide (H₂O₂) <i>in vitro</i> represents a rapid, time and cost-effective tool, commonly used as oxidative stress tantalizing the stem cell ability to cope with a hostile environment, recapitulating the onset and progression of cellular senescence. Here, H₂O₂ at different concentrations (ranging from 50 to 400 μM) and time exposures (1 or 2 hours - h), was used for the first time to compare the behavior of human Adipose tissue-derived Stem Cells (hASCs) and human Wharton's Jelly-derived MSCs (hWJ-MSCs), as representative of adult and perinatal tissue-derived stem cells, respectively. We showed timely different responses of hASCs and hWJ-MSCs at low and high subculture passages, concerning the cell proliferation, the cell senescence-associated β-Galactosidase activity, the capability of these cells to undergo passages, the morphological changes and the gene expression of <i>tumor protein p53</i> (<i>TP53</i>, alias <i>p53</i>) and <i>cyclin dependent kinase inhibitor 1A</i> (<i>CDKN1A</i>, alias <i>p21</i>) post H₂O₂ treatments. The comparison between the hASC and hWJ-MSC response to oxidative stress induced by H₂O₂ is a useful tool to assess the biological mechanisms at the basis of hMSC senescence, but it could also provide two models amenable to test <i>in vitro</i> putative anti-senescence modulators and develop anti-senescence strategies.