Pharmacological priming of adipose-derived stem cells for paracrine VEGF production with deferoxamine

Liu, Guei‐Sheung; Peshavariya, Hitesh; Higuchi, Masayoshi; Chan, Elsa C.; Dusting, Gregory J.; Jiang, Fan

doi:10.1002/term.1796

Cited by 24 publications

(28 citation statements)

References 47 publications

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“…This wash-out effect is important with regards to future in vivo applications, since it indicates a prolonged effect of the in vitro priming with DFX. Similar effects of DFX preconditioning have already been reported with regard to BM-MSCs [24] and adipose-derived stem cells (ASCs) [25]. Moreover, Agis and colleagues already reported an increased VEGF secretion after treating periodontal ligament fibroblasts with DFX [11].…”

Section: Discussionsupporting

confidence: 57%

Angiogenic Capacity of Periodontal Ligament Stem Cells Pretreated with Deferoxamine and/or Fibroblast Growth Factor-2

et al. 2016

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Periodontal ligament stem cells (PDLSCs) represent a good source of multipotent cells for cell-based therapies in regenerative medicine. The success rate of these treatments is severely dependent on the establishment of adequate vasculature in order to provide oxygen and nutrients to the transplanted cells. Pharmacological preconditioning of stem cells has been proposed as a promising method to augment their therapeutic efficacy. In this study, the aim was to improve the intrinsic angiogenic properties of PDLSCs by in vitro pretreatment with deferoxamine (DFX; 100μM), fibroblast growth factor-2 (FGF-2; 10ng/mL) or both substances combined. An antibody array revealed the differential expression of several proteins, including vascular endothelial growth factor (VEGF) and placental growth factor (PlGF). ELISA data confirmed a 1.5 to 1.8-fold increase in VEGF for all tested conditions. Moreover, 48 hours after the removal of DFX, VEGF levels remained elevated (1.8-fold) compared to control conditions. FGF-2 and combination treatment resulted in a 5.4 to 13.1-fold increase in PlGF secretion, whereas DFX treatment had no effect. Furthermore, both PDLSCs as pretreated PDLSCs induced endothelial migration. Despite the significant elevated VEGF levels of pretreated PDLSCs, the induced endothelial migration was not higher by pretreated PDLSCs. We find that the observed induced endothelial cell motility was not dependent on VEGF, since blocking the VEGFR1-3 with Axitinib (0.5nM) did not inhibit endothelial motility towards PDLSCs. Taken together, this study provides evidence that preconditioning with DFX and/or FGF-2 significantly improves the angiogenic secretome of PDLSCs, in particular VEGF and PlGF secretion. However, our data suggest that VEGF is not the only player when it comes to influencing endothelial behavior by the PDLSCs.

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Section: Discussionsupporting

confidence: 57%

Angiogenic Capacity of Periodontal Ligament Stem Cells Pretreated with Deferoxamine and/or Fibroblast Growth Factor-2

et al. 2016

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“…Low-dose UVB irradiation also upregulated bFGF, KGF, VEGF, and HGF, which enhanced the hair-regenerative potential of ASCs [15]. In addition, pharmacological priming of ASCs using deferoxamine induces HIF-1a and VEGF expression, and enhanced the migration and in vitro woundhealing activities of endothelial cells [47]. In the present study, we showed that vitamin C primarily increased HGF, IGFBP6, VEGF, bFGF, and KGF, which collectively enhanced the hairregenerative potential of ASCs.…”

Section: Discussionmentioning

confidence: 94%

“…The regenerative potential of ASCs and the paracrine effect of ASCs differ according to the stimulators used [12,15,[45][46][47]. For example, hypoxia upregulated VEGF and bFGF, which enhanced wound healing and hair-regenerative potential of ASCs [12].…”

Section: Discussionmentioning

confidence: 99%

The Molecular Mechanism Underlying the Proliferating and Preconditioning Effect of Vitamin C on Adipose-Derived Stem Cells

Kim

Sung

et al. 2014

Stem Cells and Development

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Although adipose-derived stem cells (ASCs) show promise for cell therapy, there is a tremendous need for developing ASC activators. In the present study, we investigated whether or not vitamin C increases the survival, proliferation, and hair-regenerative potential of ASCs. In addition, we tried to find the molecular mechanisms underlying the vitamin C-mediated stimulation of ASCs. Sodium-dependent vitamin C transporter 2 (SVCT2) is expressed in ASCs, and mediates uptake of vitamin C into ASCs. Vitamin C increased the survival and proliferation of ASCs in a dose-dependent manner. Vitamin C increased ERK1/2 phosphorylation, and inhibition of the mitogen-activated protein kinase (MAPK) pathway attenuated the proliferation of ASCs. Microarray and quantitative polymerase chain reaction showed that vitamin C primarily upregulated expression of proliferation-related genes, including Fos, E2F2, Ier2, Mybl1, Cdc45, JunB, FosB, and Cdca5, whereas Fos knock-down using siRNA significantly decreased vitamin C-mediated ASC proliferation. In addition, vitamin C-treated ASCs accelerated the telogen-to-anagen transition in C 3 H/HeN mice, and conditioned medium from vitamin C-treated ASCs increased the hair length and the Ki 67 -positive matrix keratinocytes in hair organ culture. Vitamin C increased the mRNA expression of HGF, IGFBP6, VEGF, bFGF, and KGF, which may mediate hair growth promotion. In summary, vitamin C is transported via SVCT2, and increased ASC proliferation is mediated by the MAPK pathway. In addition, vitamin C preconditioning enhanced the hair growth promoting effect of ASCs. Because vitamin C is safe and effective, it could be used to increase the yield and regenerative potential of ASCs.

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“…Phamacological preconditioning of stem cells to boost the release of cytoactive factors may represent the effective way to enhance their functional efficacy (14). Our experiments indicated that the paracrine effect of ASCs was significantly augmented by stimulation of media with LL-37.…”

Section: Discussionmentioning

confidence: 99%

Effects of conditioned medium from LL-37 treated adipose stem cells on human fibroblast migration

Yang

Bang

2017

Experimental and Therapeutic Medicine

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Adipose stem cell-conditioned medium may promote human dermal fibroblast (HDF) proliferation and migration by activating paracrine peptides during the re-epithelization phase of wound healing. Human antimicrobial peptide LL-37 is upregulated in the skin epithelium as part of the normal response to injury. The effects of conditioned medium (CM) from LL-37 treated adipose stem cells (ASCs) on cutaneous wound healing, including the mediation of fibroblast migration, remain to be elucidated, therefore the aim of the present study was to determine how ASCs would react to an LL-37-rich microenvironment and if CM from LL-37 treated ASCs may influence the migration of HDFs. The present study conducted migration assays with HDFs treated with CM from LL-37 treated ASCs. Expression of CXC chemokine receptor 4 (CXCR4), which controls the recruitment of HDFs, was analyzed at the mRNA and protein levels. To further characterize the stimulatory effects of LL-37 on ASCs, the expression of stromal cell-derived factor-1α (SDF-1α), a CXC chemokine, was investigated. CM from LL-37-treated ASCs induced migration of HDFs in a time- and dose-dependent manner, with a maximum difference in migration observed 24 h following stimulation with LL-37 at a concentration of 10 µg/ml. The HDF migration and the expression of CXCR4 in fibroblasts was markedly increased upon treatment with CM from LL-37-treated ASCs compared with CM from untreated ASCs. SDF-1α expression was markedly increased in CM from LL-37 treated ASCs. It was additionally observed that SDF-1α blockade significantly reduced HDF migration. These findings suggest the feasibility of CM from LL-37-treated ASCs as a potential therapeutic for human dermal fibroblast migration.

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Pharmacological priming of adipose-derived stem cells for paracrine VEGF production with deferoxamine

Cited by 24 publications

References 47 publications

Angiogenic Capacity of Periodontal Ligament Stem Cells Pretreated with Deferoxamine and/or Fibroblast Growth Factor-2

Angiogenic Capacity of Periodontal Ligament Stem Cells Pretreated with Deferoxamine and/or Fibroblast Growth Factor-2

The Molecular Mechanism Underlying the Proliferating and Preconditioning Effect of Vitamin C on Adipose-Derived Stem Cells

Effects of conditioned medium from LL-37 treated adipose stem cells on human fibroblast migration

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