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.

Preconditioning of adipose tissue-derived mesenchymal stem cells with deferoxamine increases the production of pro-angiogenic, neuroprotective and anti-inflammatory factors: Potential application in the treatment of diabetic neuropathy

“…We chose these doses of DFX since it has been previously reported that, for others stem cells types, the incubation with this dose range improves their therapeutic potential and has only a modest impact on stem cells survival [31, 32]. We observed that 48 hours of preconditioning did not induce cell morphology changes (Fig 2A) and did not significantly reduce cell survival (Fig 2B) (6.82x10 5 ± 0.20x10 5 cells after preconditioning with 150μM DFX; 6.83x10 5 ± 0.22x10 5 cells after preconditioning with 400μM DFX compared to 7.95x10 5 ± 0.43x10 5 cells in the non-preconditioned condition), suggesting that 48 hours of preconditioning with 150μM or 400μM of DFX have nontoxic effects on MSCs.…”

Analysis of Metabolomic Changes in Mesenchymal Stem Cells on Treatment with Desferrioxamine as a Hypoxia Mimetic Compared with Hypoxic Conditions

“…However, DFO also produces hydroxyl radicals and has been reported to function as a pro-oxidant [8]. To date, various studies have focused on the usefulness of DFO in culturing MSCs; DFO preconditioning of neural-like cells derived from Wharton's Jelly improved their tolerance and therapeutic potential, and was demonstrated to be useful for cell therapy [9]. Moreover, preconditioning MSCs with DFO prior to transplantation has been shown to improve the efficiency of MSC homing, improving cell therapy efficiency [10], while enhancement of endothelial progenitor cell homing [11] in conjunction with treating neural stem cells with DFO has been reported to protect the brain from ischemia and other conditions [12]; however, further study is required.…”

Comparison of Oxidative Stress Effects on Senescence Patterning of Human Adult and Perinatal Tissue-Derived Stem Cells in Short and Long-term Cultures

“…Moreover, H 2 O 2 treatment provokes DNA breaks 41 , raises SA β-Gal positive cells 42 , alters the expression of senescent marker genes, as well as p53 , p21 , mitogen-activated protein kinase 14 ( MAPK14 , alias p38 ) and sirtuin 1 ( SIRT1 ) 38 , 39 , 42 , and increases apoptosis with a decline of pro-survival gene expression 38 . It has been recently shown that also human Wharton's Jelly-derived MSCs (hWJ-MSCs) treated with H 2 O 2 undergo premature senescence at early culture passages: these cells show typical changes in morphology 43 , slow their proliferation 44 , 45 , result positive for SA β-Gal 43 , 44 , express typical senescence 43 and pro-apoptotic gene markers, while displaying a down-regulation of survival genes 44 , 46 .…”