DIFFERENCES IN DEFENSE MECHANISMS AGAINST OXIDATIVE STRESS IN BOTH HUMAN EMBRYONIC AND ENDOMETRIUM-DERIVED
MESENCHYMAL STEM CELLS
A.V. Borodkina,1 A.N. Shatrova, N.A. Pugovkina, V.I .Zemelko,
N.N. Nikolsky, E.B. Burova
Institute of Cytology RAS, St. Petersburg;
1 e-mail: springwater@mail.ru
Oxidative stress has been shown to induce either apoptosis or stress-induced premature senescence (SIPS) in different cell types. At present, it is generally accepted that stem
cells have high resistance to oxidative stress, however data reported by various authors are controversial. In this study, we investigated stress responses of human embryonic stem cells
(hESC) and human mesenchymal stem cells (hMESC) derived from desquamated endometrium to hydrogen peroxide (Í2Î2). Cell viability was evaluated by
MTT assay. LD50 were determined as 300–350; 350–400 and 600–700 µM for hESC, human embryonic fibroblasts and hMESC, respectively. Thus, among the cell lines
studied, hMESC demonstrated the most resistance to increased Í2Î2 concentration. We found for the first time that sub-lethal doses of
Í2Î2 induced premature senescence phenotype in hMESC, like in HEF, that was characterized by increased expression of cyclin-dependent kinase inhibitor
p21Waf1/Cip1, an irreversible cell cycle arrest, the permanent loss of proliferative potential, cell hypertrophy and SA-β-Gal staining. While a sub-lethal
Í2Î2 dose (200 µM) promoted in hMESC only SIPS, the higher Í2Î2 doses induced also apoptosis in the part of the cell population.
On the contrary, in hESC, Í2Î2 regardless of the doses tested (from 50 to 500 µM) triggered apoptosis, that was the only pronounced response of these cells
to oxidative damage. The data obtained demonstrate that stem cells of various origins under oxidative stress utilize the different defense mechanisms: hESC rapidly eliminate damaged
cells through apoptosis, whereas hMESC may enter SIPS.
Key words: cells, oxidative stress, premature senescence, apoptosis
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