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 ex vivo to increase cell number prior to transplantation, which unfortunately leads to cell senescence, hampering post-transplant outcomes. Hydrogen peroxide (H 2 O 2 ) in vitro 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, H 2 O 2 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 tumor protein p53 (TP53, alias p53) and cyclin dependent kinase inhibitor 1A (CDKN1A, alias p21) post H 2 O 2 treatments. The comparison between the hASC and hWJ-MSC response to oxidative stress induced by H 2 O 2 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 in vitro putative anti-senescence modulators and develop anti-senescence strategies.