Overexpression of Vascular Endothelial Growth Factor In Vitro Using Deferoxamine: A New Drug to Increase Islet Vascularization During Transplantation

Langlois, A.; Bietiger, W.; Mandes, K.; Maillard, Élisa; Belcourt, A.; Pinget, M.; Kessler, L.; Sigrist, S.

doi:10.1016/j.transproceed.2008.01.003

Cited by 27 publications

(13 citation statements)

References 8 publications

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“…As expected, these treatments induced the stabilization of HIF-1α, and led to the overexpression of genes related to pro-angiogenic responses including VEGFα and ANG-1. These results are in agreement with earlier studies indicating that DFX can induce VEGFα expression in various cell types, such as pancreatic beta cells [54], endothelial cells [55], and bone marrow stromal cells [33]. However, we also observed that the preconditioning of MSCs with DFX could also increase the expression of potent neuroprotective factors including NGF, GDNF and NT-3, and cytokines with anti-inflammatory activity such as IL4 and IL5.…”

Section: Discussionsupporting

confidence: 93%

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

et al. 2017

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Diabetic neuropathy (DN) is one of the most frequent and troublesome complications of diabetes mellitus. Evidence from diabetic animal models and diabetic patients suggests that reduced availability of neuroprotective and pro-angiogenic factors in the nerves in combination with a chronic pro-inflammatory microenvironment and high level of oxidative stress, contribute to the pathogenesis of DN. Mesenchymal stem cells (MSCs) are of great interest as therapeutic agents for regenerative purposes, since they can secrete a broad range of cytoprotective and anti-inflammatory factors. Therefore, the use of the MSC secretome may represent a promising approach for DN treatment. Recent data indicate that the paracrine potential of MSCs could be boosted by preconditioning these cells with an environmental or pharmacological stimulus, enhancing their therapeutic efficacy. In the present study, we observed that the preconditioning of human adipose tissue-derived MSCs (AD-MSCs) with 150μM or 400μM of the iron chelator deferoxamine (DFX) for 48 hours, increased the abundance of the hypoxia inducible factor 1 alpha (HIF-1α) in a concentration dependent manner, without affecting MSC morphology and survival. Activation of HIF-1α led to the up-regulation of the mRNA levels of pro-angiogenic factors like vascular endothelial growth factor alpha and angiopoietin 1. Furthermore this preconditioning increased the expression of potent neuroprotective factors, including nerve growth factor, glial cell-derived neurotrophic factor and neurotrophin-3, and cytokines with anti-inflammatory activity like IL4 and IL5. Additionally, we observed that these molecules, which could also be used as therapeutics, were also increased in the secretome of MSCs preconditioned with DFX compared to the secretome obtained from non-preconditioned cells. Moreover, DFX preconditioning significantly increased the total antioxidant capacity of the MSC secretome and they showed neuroprotective effects when evaluated in an in vitro model of DN. Altogether, our findings suggest that DFX preconditioning of AD-MSCs improves their therapeutic potential and should be considered as a potential strategy for the generation of new alternatives for DN treatment.

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Section: Discussionsupporting

confidence: 93%

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

et al. 2017

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“…Earlier studies have shown success in HIF-1a stabilization followed by DFO treatment (Xiao et al 2013). Also these results are in consistent with earlier studies, indicating that DFO can induce VEGF up-regulation in various cell types, such as beta cells (Langlois et al 2008), alveolar epithelial cells (Pham et al 2002), endothelial cells (Yamakawa et al 2003), and bone marrow stromal cells (Potier et al 2008). Fig.…”

Section: Discussionsupporting

confidence: 89%

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

et al. 2015

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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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“…The protease inhibitor a1-antitrypsin inhibits thrombin, and promotes early graft survival [171]. The iron chelator deferoxamine is an antioxidant used during islet isolation, that may also promote vascularization of grafts [172].…”

Section: Loss Of Beta Cells During Islet Isolation and Primary Non-fumentioning

confidence: 99%

Beta cell apoptosis in diabetes

et al. 2009

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Apoptosis of beta cells is a feature of both type 1 and type 2 diabetes as well as loss of islets after transplantation. In type 1 diabetes, beta cells are destroyed by immunological mechanisms. In type 2 diabetes abnormal levels of metabolic factors contribute to beta cell failure and subsequent apoptosis. Loss of beta cells after islet transplantation is due to many factors including the stress associated with islet isolation, primary graft non-function and allogeneic graft rejection. Irrespective of the exact mediators, highly conserved intracellular pathways of apoptosis are triggered. This review will outline the molecular mediators of beta cell apoptosis and the intracellular pathways activated.

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Overexpression of Vascular Endothelial Growth Factor In Vitro Using Deferoxamine: A New Drug to Increase Islet Vascularization During Transplantation

Cited by 27 publications

References 8 publications

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

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

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

Beta cell apoptosis in diabetes

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