title: Angiogenic Capacity of Periodontal Ligament Stem Cells Pretreated with Deferoxamine and/or Fibroblast Growth Factor-2.
abstract: 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.
authors.affiliation: Morphology Research Group, Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium.
authors.forename: Jessica
authors.initials: J
authors.lastname: Ratajczak
authors.affiliation: Morphology Research Group, Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium.
authors.forename: Petra
authors.initials: P
authors.lastname: Hilkens
authors.affiliation: Morphology Research Group, Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium.
authors.forename: Pascal
authors.initials: P
authors.lastname: Gervois
authors.affiliation: Morphology Research Group, Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium.
authors.forename: Esther
authors.initials: E
authors.lastname: Wolfs
authors.affiliation: Oral Imaging Center, OMFS-IMPATH Research Group, Department of Imaging and Pathology, Faculty of Medicine, University of Leuven, Leuven, Belgium.
authors.forename: Reinhilde
authors.initials: R
authors.lastname: Jacobs
authors.affiliation: Morphology Research Group, Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium.
authors.forename: Ivo
authors.initials: I
authors.lastname: Lambrichts
authors.affiliation: Morphology Research Group, Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium.
authors.forename: Annelies
authors.initials: A
authors.lastname: Bronckaers
mesh_terms: D000293:Adolescent; D000328:Adult; D043925:Angiogenesis Inducing Agents / Q000494:pharmacology; D000818:Animals; D018929:Cell Culture Techniques; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D002645:Chickens; D003676:Deferoxamine / Q000494:pharmacology*; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006801:Humans; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010513:Periodontal Ligament / Q000166:cytology* / Q000187:drug effects*; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects*; D055815:Young Adult
chemical_list: D043925:Angiogenesis Inducing Agents; D016222:Fibroblast Growth Factor 2; D003676:Deferoxamine