title: Deferoxamine Preconditioning of Neural-Like Cells Derived from Human Wharton's Jelly Mesenchymal Stem Cells as a Strategy to Promote Their Tolerance and Therapeutic Potential: An In Vitro Study.
abstract: Transplantation of neural-like 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 factor-1 (HIF-1) 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 neural-like cells derived from human Wharton's jelly mesenchymal stem cells (HWJ-MSCs) in presence of hydrogen peroxide (H2O2). HWJ-MSCs were differentiated toward neural-like cells for 14 days and neural cell markers were identified using immunocytochemistry. HWJ-MSC-derived neural-like cells were then treated with 100 µM DFO, as a known hypoxia mimetic agent for 48 h. mRNA and protein expression of HIF-1 target genes including brain-derived neurotrophic factors (BDNF) and vascular endothelial growth factor (VEGF) significantly increased using RT-PCR and Western blotting which were reversed by HIF-1α inhibitor, while, gene expression of Akt-1, Bcl-2, and Bax did not change significantly but pAkt-1 was up-regulated as compared to poor DFO group. However, addition of H2O2 to DFO-treated cells resulted in higher resistance to H2O2-induced cell death. Western blotting analysis also showed significant up-regulation of HIF-1α, BDNF, VEGF, and pAkt-1, and decrease of Bax/Bcl-2 ratio as compared to poor DFO. These results may suggest that DFO preconditioning of HWJ-MSC-derived neural-like cells improves their tolerance and therapeutic potential and might be considered as a valuable strategy to improve cell therapy.
authors.affiliation: Razi Drug Research Center, Department of Pharmacology, School of Medicine, Iran University of Medical Science, Tehran, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Nouri
authors.affiliation: Department of Anatomy, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran.
authors.forename: Parvin
authors.initials: P
authors.lastname: Salehinejad
authors.affiliation: Department of Anatomy, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran.
authors.forename: Seyed Noureddin
authors.initials: SN
authors.lastname: Nematollahi-Mahani
authors.affiliation: Tissue Engineering Group (TEG) and Research, National Orthopedic Centre of Excellence in Research and Learning (NOCERAL), Department of Orthopedics, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Tunku
authors.initials: T
authors.lastname: Kamarul
authors.affiliation: Department of Neuroscience, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Zarrindast
authors.affiliation: Razi Drug Research Center, Department of Pharmacology, School of Medicine, Iran University of Medical Science, Tehran, Iran. sharifal@yahoo.com.|Tissue Engineering Group (TEG) and Research, National Orthopedic Centre of Excellence in Research and Learning (NOCERAL), Department of Orthopedics, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. sharifal@yahoo.com.|Department of Tissue Engineering and Regenerative Medicine, School of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran. sharifal@yahoo.com.
authors.forename: Ali Mohammad
authors.initials: AM
authors.lastname: Sharifi
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003676:Deferoxamine / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D059631:Wharton Jelly / Q000187:drug effects*
chemical_list: D006861:Hydrogen Peroxide; D003676:Deferoxamine
keywords: BDNF; Deferoxamine; Neural-like cells; Preconditioning; VEGF