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

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2016 Dec 10

PMID 27936076

Citations 13

Authors

Jessica Ratajczak

Petra Hilkens

Pascal Gervois

Esther Wolfs

Reinhilde Jacobs

Ivo Lambrichts

Annelies Bronckaers

Affiliations

Soon will be listed here.

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.

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References

Seo B, Miura M, Gronthos S, Bartold P, Batouli S, Brahim J . Investigation of multipotent postnatal stem cells from human periodontal ligament. Lancet. 2004; 364(9429):149-55. DOI: 10.1016/S0140-6736(04)16627-0. View

Potier E, Ferreira E, Dennler S, Mauviel A, Oudina K, Logeart-Avramoglou D . Desferrioxamine-driven upregulation of angiogenic factor expression by human bone marrow stromal cells. J Tissue Eng Regen Med. 2008; 2(5):272-8. DOI: 10.1002/term.92. View

Ades E, Candal F, Swerlick R, George V, Summers S, Bosse D . HMEC-1: establishment of an immortalized human microvascular endothelial cell line. J Invest Dermatol. 1992; 99(6):683-90. DOI: 10.1111/1523-1747.ep12613748. View

Lee M, Kim J, Yang E . Hinokitiol activates the hypoxia-inducible factor (HIF) pathway through inhibition of HIF hydroxylases. Biochem Biophys Res Commun. 2010; 396(2):370-5. DOI: 10.1016/j.bbrc.2010.04.099. View

Hilkens P, Fanton Y, Martens W, Gervois P, Struys T, Politis C . Pro-angiogenic impact of dental stem cells in vitro and in vivo. Stem Cell Res. 2014; 12(3):778-90. DOI: 10.1016/j.scr.2014.03.008. View

Rosova I, Dao M, Capoccia B, Link D, Nolta J . Hypoxic preconditioning results in increased motility and improved therapeutic potential of human mesenchymal stem cells. Stem Cells. 2008; 26(8):2173-82. PMC: 3017477. DOI: 10.1634/stemcells.2007-1104. View

Osathanon T, Vivatbutsiri P, Sukarawan W, Sriarj W, Pavasant P, Sooampon S . Cobalt chloride supplementation induces stem-cell marker expression and inhibits osteoblastic differentiation in human periodontal ligament cells. Arch Oral Biol. 2014; 60(1):29-36. DOI: 10.1016/j.archoralbio.2014.08.018. View

Distler J, Hirth A, Kurowska-Stolarska M, Gay R, Gay S, Distler O . Angiogenic and angiostatic factors in the molecular control of angiogenesis. Q J Nucl Med. 2003; 47(3):149-61. View

Yanagita M, Kojima Y, Kubota M, Mori K, Yamashita M, Yamada S . Cooperative effects of FGF-2 and VEGF-A in periodontal ligament cells. J Dent Res. 2013; 93(1):89-95. PMC: 3872850. DOI: 10.1177/0022034513511640. View

10.

Muller H, Cvikl B, Gruber R, Watzek G, Agis H . Prolyl hydroxylase inhibitors increase the production of vascular endothelial growth factor in dental pulp-derived cells. J Endod. 2012; 38(11):1498-503. DOI: 10.1016/j.joen.2012.08.003. View

11.

Chimote G, Sreenivasan J, Pawar N, Subramanian J, Sivaramakrishnan H, Sharma S . Comparison of effects of anti-angiogenic agents in the zebrafish efficacy-toxicity model for translational anti-angiogenic drug discovery. Drug Des Devel Ther. 2014; 8:1107-23. PMC: 4145829. DOI: 10.2147/DDDT.S55621. View

12.

Potier E, Ferreira E, Andriamanalijaona R, Pujol J, Oudina K, Logeart-Avramoglou D . Hypoxia affects mesenchymal stromal cell osteogenic differentiation and angiogenic factor expression. Bone. 2007; 40(4):1078-87. DOI: 10.1016/j.bone.2006.11.024. View

13.

Liu L, Gao J, Yuan Y, Chang Q, Liao Y, Lu F . Hypoxia preconditioned human adipose derived mesenchymal stem cells enhance angiogenic potential via secretion of increased VEGF and bFGF. Cell Biol Int. 2013; 37(6):551-60. DOI: 10.1002/cbin.10097. View

14.

Nokhbehsaim M, Keser S, Nogueira A, Cirelli J, Jepsen S, Jager A . Beneficial effects of adiponectin on periodontal ligament cells under normal and regenerative conditions. J Diabetes Res. 2014; 2014:796565. PMC: 4120919. DOI: 10.1155/2014/796565. View

15.

Caplan A . Adult mesenchymal stem cells for tissue engineering versus regenerative medicine. J Cell Physiol. 2007; 213(2):341-7. DOI: 10.1002/jcp.21200. View

16.

Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D . Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006; 8(4):315-7. DOI: 10.1080/14653240600855905. View

17.

Yeasmin S, Ceccarelli J, Vigen M, Carrion B, Putnam A, Tarle S . Stem cells derived from tooth periodontal ligament enhance functional angiogenesis by endothelial cells. Tissue Eng Part A. 2013; 20(7-8):1188-96. PMC: 3993081. DOI: 10.1089/ten.TEA.2013.0512. View

18.

Nakamura S, Yamada Y, Baba S, Kato H, Kogami H, Takao M . Culture medium study of human mesenchymal stem cells for practical use of tissue engineering and regenerative medicine. Biomed Mater Eng. 2008; 18(3):129-36. View

19.

Liu G, Peshavariya H, Higuchi M, Chan E, Dusting G, Jiang F . Pharmacological priming of adipose-derived stem cells for paracrine VEGF production with deferoxamine. J Tissue Eng Regen Med. 2013; 10(3):E167-76. DOI: 10.1002/term.1796. View

20.

Agis H, Watzek G, Gruber R . Prolyl hydroxylase inhibitors increase the production of vascular endothelial growth factor by periodontal fibroblasts. J Periodontal Res. 2011; 47(2):165-73. DOI: 10.1111/j.1600-0765.2011.01415.x. View