title: The Combination of Vascular Endothelial Growth Factor and Stromal Cell-Derived Factor Induces Superior Angiogenic Sprouting by Outgrowth Endothelial Cells.
abstract: Endothelial progenitor cells are being broadly explored for the treatment of ischemic cardiovascular diseases, but their response to molecules commonly used to promote the growth of new blood vessels has not been fully characterized. In this study, angiogenic sprout formation in a 3-dimensional, in vitro model by one type of endothelial progenitor, outgrowth endothelial cells (OECs), was characterized in response to exposure to stromal cell-derived factor (SDF) and vascular endothelial growth factor (VEGF) and then compared to mature endothelial cells. Exposure to SDF alone did not increase angiogenic sprouting in comparison to control media, while a combination of VEGF and SDF demonstrated greater potency than VEGF alone for all cell types. Together, VEGF and SDF reduced the sprout initiation time and maintained sprouting levels over time. In direct competition with mature endothelial cells, OECs preferentially localized to the tip cell position, suggesting an enhanced sprouting potential. Overall, these results reveal the impact of the combination of VEGF and SDF on endothelial cell sprouting, and support the enhanced potential of OECs, as opposed to mature endothelial cells, for treating ischemic diseases.
authors.affiliation: School of Engineering and Applied Sciences, Harvard University, Cambridge, Mass., USA.
authors.forename: Erin M
authors.initials: EM
authors.lastname: Anderson
authors.forename: David J
authors.initials: DJ
authors.lastname: Mooney
mesh_terms: D018929:Cell Culture Techniques; D002455:Cell Division; D054377:Chemokine CXCL12 / Q000494:pharmacology* / Q000502:physiology; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects*; D005312:Fetal Blood / Q000166:cytology; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008863:Microspheres; D055806:Microvessels / Q000166:cytology; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011994:Recombinant Proteins / Q000494:pharmacology; D059008:Time-Lapse Imaging; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology* / Q000502:physiology
chemical_list: C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D011994:Recombinant Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A