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Purpose:  To investigate the protective effect of preconditioning with non-toxic dose of hydrogen peroxide (H 2 O 2 ) as a possible cell signaling molecule, against cell death induced by toxic concentration of H 2 O 2 or by serum deprivation in human Wharton's jelly-derived mesenchymal stem cells (HWJ-MSCs) and underlying mechanisms.  Methods:  HWJ-MSCs were isolated and identified using flow cytometry. After finding non-toxic concentration of H 2 O 2 , cells preconditioning was performed by H 2 O 2 (20 μM) for 12 h and cell tolerance against serum deprivation or toxic levels of H 2 O 2 was assayed by MTT test. Effect of preconditioning on mRNA and protein expression of Akt-1, Bcl-2 and Bax were examined using reverse transcription polymerase chain reaction (RT-PCR) and western blotting respectively. Role of hypoxia-inducible factor (HIF)-1α was explored in presence HIF-1α inhibitor.  Results:  Preconditioning with 20 μM H 2 O 2 for 12 h was non-toxic and decreased cell death induced by oxidative stress and serum deprivation in MSC cultures. However, the increased tolerance reversed in the presence of inhibitor of HIF-1α. By regards to RT-PCR and western blotting data, although expression of Akt-1, Bcl-2 and Bax was not change considerably but phosphorylated Akt-1 (pAkt-1) was up regulated after treatment with 20 μM H 2 O 2 compared to control group. Moreover after exposure to 100 μM H 2 O 2 , western blotting analysis showed that cell pretreatment with 20 μM H 2 O 2 , decremented Bax/Bcl2 ratio and up-regulated HIF-1α and pAkt-1 compared to the control group.  Conclusion:  Increased tolerance of H 2 O 2 -pretreated cells led to the suggestion that transplantation of H 2 O 2 preconditioned MSCs may improve therapeutic potential of stem cells in cell therapy procedures.

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Preconditioning of Mesenchymal Stem Cells with Non-ToxicConcentration of Hydrogen Peroxide Against Oxidative StressInduced Cell Death: The Role of Hypoxia-Inducible Factor-1