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Int J Med Sci. 2018 Oct 20;15(13):1486-1501. doi: 10.7150/ijms.27181. eCollection 2018.

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

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Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Via Massarenti 9, 40138 Bologna, Italy.
National Laboratory of Molecular Biology and Stem Cell Bioengineering of the National Institute of Biostructures and Biosystems (NIBB) - Eldor Lab, at the Innovation Accelerator, CNR, Via Piero Gobetti 101, 40129 Bologna, Italy.
Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/B, 07100 Sassari, Italy.
Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche (CNR), Monserrato, 09042 Cagliari, Italy.


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 (H2O2) 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, 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 tumor protein p53 (TP53, alias p53) and cyclin dependent kinase inhibitor 1A (CDKN1A, alias p21) 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 in vitro putative anti-senescence modulators and develop anti-senescence strategies.


Resazurin-based assay; cell senescence; human mesenchymal stem cells; hydrogen peroxide; oxidative stress-induced premature senescence; senescence-associated β-galactosidase activity

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