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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

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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.

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Acknowledgments

The 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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Authors and Affiliations

  1. Razi Drug Research Center, Department of Pharmacology, School of Medicine, Iran University of Medical Science, Tehran, Iran

    Fatemeh Nouri & Ali Mohammad Sharifi

  2. Department of Anatomy, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran

    Parvin Salehinejad & Seyed Noureddin Nematollahi-mahani

  3. 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

    Tunku Kamarul & Ali Mohammad Sharifi

  4. Department of Neuroscience, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Mohammad Reza Zarrindast

  5. Department of Tissue Engineering and Regenerative Medicine, School of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran

    Ali Mohammad Sharifi

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  1. Fatemeh Nouri
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  2. Parvin Salehinejad
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Correspondence to Ali Mohammad Sharifi.

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Nouri, F., Salehinejad, P., Nematollahi-mahani, S.N. et al. 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. Cell Mol Neurobiol 36, 689–700 (2016). https://doi.org/10.1007/s10571-015-0249-8

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