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

• Published in: PloS one 2016-12, Vol.11 (12), p.e0167807-e0167807
• Main Authors: Ratajczak, Jessica, Hilkens, Petra, Gervois, Pascal, Wolfs, Esther, Jacobs, Reinhilde, Lambrichts, Ivo, Bronckaers, Annelies
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Angiogenesis; Angiogenesis Inducing Agents - pharmacology; Animals; Biology and Life Sciences; Biomedical research; Cell Culture Techniques; Cell Movement - drug effects; Cells, Cultured; Chickens; Consent; Deferoxamine; Deferoxamine - pharmacology; Endothelial cells; Endothelial Cells - cytology; Endothelial Cells - drug effects; Endothelium; Enzyme-linked immunosorbent assay; Extracellular matrix; Fibroblast growth factor 2; Fibroblast Growth Factor 2 - pharmacology; Fibroblast growth factors; Fibroblasts; Health aspects; Humans; Hypoxia; Ligaments; Medical research; Medicin och hälsovetenskap; Medicine; Medicine and Health Sciences; Mesenchymal stem cells; Morphology; Neovascularization, Physiologic - drug effects; Nutrients; Oxygen; Periodontal ligament; Periodontal Ligament - cytology; Periodontal Ligament - drug effects; Pharmacology; Physiological aspects; Placenta; Preconditioning; Proteins; Regenerative medicine; Secretion; Secretome; Stem cells; Stem Cells - cytology; Stem Cells - drug effects; Studies; Tissue engineering; Tumor necrosis factor-TNF; Vascular endothelial growth factor; Young Adult
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0167807

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.