Deferoxamine Preconditioning of NeuralLike Cells

Authors: Fatemeh Nouri Parvin Salehinejad Seyed Noureddin Nematollahimahani Tunku Kamarul Mohammad Reza Zarrindast Ali Mohammad Sharifi

Publish Date: 2015/08/05

Volume: 36, Issue: 5, Pages: 689-700

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Abstract

Transplantation of neurallike cells is considered as a promising therapeutic strategy developed for neurodegenerative disease in particular for ischemic stroke Since cell survival is a major concern following cell implantation a number of studies have underlined the protective effects of preconditioning with hypoxia or hypoxia mimetic pharmacological agents such as deferoxamine DFO induced by activation of hypoxia inducible factor1 HIF1 and its target genes The present study has investigated the effects of DFO preconditioning on some factors involved in cell survival angiogenesis and neurogenesis of neurallike cells derived from human Wharton’s jelly mesenchymal stem cells HWJMSCs in presence of hydrogen peroxide H2O2 HWJMSCs were differentiated toward neurallike cells for 14 days and neural cell markers were identified using immunocytochemistry HWJMSCderived neurallike cells were then treated with 100 µM DFO as a known hypoxia mimetic agent for 48 h mRNA and protein expression of HIF1 target genes including brainderived neurotrophic factors BDNF and vascular endothelial growth factor VEGF significantly increased using RTPCR and Western blotting which were reversed by HIF1α inhibitor while gene expression of Akt1 Bcl2 and Bax did not change significantly but pAkt1 was upregulated as compared to poor DFO group However addition of H2O2 to DFOtreated cells resulted in higher resistance to H2O2induced cell death Western blotting analysis also showed significant upregulation of HIF1α BDNF VEGF and pAkt1 and decrease of Bax/Bcl2 ratio as compared to poor DFO These results may suggest that DFO preconditioning of HWJMSCderived neurallike cells improves their tolerance and therapeutic potential and might be considered as a valuable strategy to improve cell therapyThe authors especially thank S Tavakol from Department of pharmacology Iran University of Medical sciences Tehran Iran and F Pour Seyedi Department of Anatomy Kerman University of Medical science Kerman Iran for valuable assistance This work was financially supported by Iran University of Medical Sciences and HIR grant from University of Malaya

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