Abstract
Angiogenesis, the formation of capillaries from pre-existing blood vessels, is a key process in tissue engineering. If blood supply cannot be established rapidly, there is insufficient oxygen and nutrient transport and necrosis of the implanted tissue will occur. Recent studies indicate that the human dental pulp contains precursor cells, named dental pulp stem cells (hDPSC) that show self-renewal and multilineage differentiation capacity. Since these cells can be easily isolated, cultured and cryopreserved, they represent an attractive stem cell source for tissue engineering. Until now, only little is known about the angiogenic abilities and mechanisms of the hDPSC. In this study, the angiogenic profile of both cell lysates and conditioned medium of hDPSC was determined by means of an antibody array. Numerous pro-and anti-angiogenic factors such as vascular endothelial growth factor (VEGF), monocyte chemotactic protein-1 (MCP-1), plasminogen activator inhibitor-1 (PAI-1) and endostatin were found both at the mRNA and protein level. hDPSC had no influence on the proliferation of the human microvascular endothelial cells (HMEC-1), but were able to significantly induce HMEC-1 migration in vitro. Addition of the PI3K-inhibitor LY294002 and the MEK-inhibitor U0126 to the HMEC-1 inhibited this effect, suggesting that both Akt and ERK pathways are involved in hDPSC-mediated HMEC-1 migration. Antibodies against VEGF also abolished the chemotactic actions of hDPSC. Furthermore, in the chicken chorioallantoic membrane (CAM) assay, hDPSC were able to significantly induce blood vessel formation. In conclusion, hDPSC have the ability to induce angiogenesis, meaning that this stem cell population has a great clinical potential, not only for tissue engineering but also for the treatment of chronic wounds, stroke and myocardial infarctions.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adolescent
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Angiogenesis Inducing Agents / metabolism*
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Angiogenesis Inducing Agents / pharmacology
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Animals
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Butadienes / pharmacology
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Cell Line
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Cell Movement / drug effects
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Cells, Cultured
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Chemokine CCL2 / genetics
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Chemokine CCL2 / metabolism
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Chick Embryo
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Chorioallantoic Membrane / blood supply
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Chorioallantoic Membrane / drug effects
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Chromones / pharmacology
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Culture Media, Conditioned / metabolism
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Culture Media, Conditioned / pharmacology
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Dental Pulp / cytology*
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Endostatins / genetics
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Endostatins / metabolism
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Endothelial Cells / cytology
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Endothelial Cells / drug effects
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Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
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Extracellular Signal-Regulated MAP Kinases / metabolism
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Humans
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Immunohistochemistry
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Morpholines / pharmacology
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Neovascularization, Physiologic / drug effects
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Neovascularization, Physiologic / physiology*
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Nitriles / pharmacology
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Phosphatidylinositol 3-Kinases / metabolism
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Phosphoinositide-3 Kinase Inhibitors
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Plasminogen Activator Inhibitor 1 / genetics
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Plasminogen Activator Inhibitor 1 / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Stem Cells / metabolism*
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Vascular Endothelial Growth Factor A / genetics
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Vascular Endothelial Growth Factor A / metabolism
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Young Adult
Substances
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Angiogenesis Inducing Agents
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Butadienes
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CCL2 protein, human
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Chemokine CCL2
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Chromones
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Culture Media, Conditioned
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Endostatins
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Morpholines
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Nitriles
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Phosphoinositide-3 Kinase Inhibitors
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Plasminogen Activator Inhibitor 1
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U 0126
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Vascular Endothelial Growth Factor A
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2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
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Extracellular Signal-Regulated MAP Kinases
Grants and funding
This research was supported by grants to A.B. from the Research Foundation-Flanders (‘Fonds Wetenschappelijk onderzoek Vlaanderen- FWO’, grant Nr. 1.5.060.13N). P.H. benefits from a PhD scholarship of the FWO and A.B. is a postdoctoral fellow of the FWO. The funder (FWO) has no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.