H2O2-preconditioned mesenchymal stem cell regenerative effects on acute liver failure mice

Mesenchymal stem cells (MSCs) are attractive cells for cell therapy. However, the efficacy of MSCs is limited because of low survival rate following translation. In this study, MSCs were preconditioned with sub-lethal doses of H2O2. The therapeutic potential of preconditioning MSCs was examined on acute liver failure in mice. In the present experimental study, MSCs were isolated from bone marrow aspirate. Cells from passage four were treated with different concentrations of H2O2 for 24 hrs, and then were recovered in fresh medium for 7 hrs followed by exposure to lethal doses of H2O2. Cell viability was measured with WST-1 assay. In the in vivo phase, acute liver failure was induced by CCl4; then, the regenerative potential of preconditioned-MSCs was evaluated using biochemical as well as histological methods. Survival rates were higher in the engrafted mice with preconditioned-MSCs in comparison to those who received normal MSCs. Three days after cell therapy liver enzymes reached the normal level in engrafted group with preconditioned-MSCs. Interestingly, histological results revealed a significant improvement in liver regeneration potential in transplanted groups with preconditioned-MSCs. Preconditioning of MSCs with H2O2 not only enhances their survival but also increases the efficacy of MSC-based cell therapy in liver acute failure.