Journal Article

Effects of combinations of BMP-2 with FGF-2 and/or VEGF on HUVECs angiogenesis in vitro and CAM angiogenesis in vivo

Liao, Xiaoming, Pu, Ximing, Yao, Yadong, Leng, Yue, Chen, Xianchun, Bai, Yan, Yin, Guangfu, Huang, Zhongbing

2014

Overview

Angiogenesis, a complex biologic process, is regulated by a large number of angiogenic factors, including vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2). Whether Bone morphogenetic proteins-2 (BMP-2), the osteoinductive factor, could significantly reinforce the effect of VEGF and FGF-2 on angiogenesis has not been studied in detail. To study the positive effects of multiple growth factors on angiogenesis, HUVECs were treated with BMP-2, VEGF, or FGF-2 singly and in binary and ternary combinations. This study further investigates the optimal timing of the ternary combination of BMP-2, VEGF and FGF-2 for angiogenesis in the chorioallantoic membrane (FGF-2 CAM). Results of single applications of BMP-2, VEGF, or FGF-2 suggested that HUVECs angiogenesis could be promoted in a dose-dependent manner and that the optimal concentration of BMP, VEGF and FGF-2 was 10, 50 and 1 ng/mL, respectively. These results indicated that the angiogenic activity of VEGF and FGF-2 was amplified by combining with BMP-2. The ternary combination of BMP-2, VEGF and FGF-2 exhibited a positive and synergistic effect on HUVECs angiogenesis, with the lower concentrations of each factor (1 ng/mL of BMP-2, 25 ng/mL of VEGF and 0.1 ng/mL of FGF-2) being sufficient to show synergistic promotion. When VEGF and FGF-2 were added in the initial activation stage and BMP-2 was added in the maturation stage, both HUVECs angiogenesis in vitro and CAM angiogenesis in vivo could be enhanced more effectively. These results could provide a basis for the controlled release systems capable of delivering multiple factors sequentially to promote angiogenesis in tissue engineering.

• Publisher: Springer-Verlag,Springer Berlin Heidelberg,Springer,Springer Nature B.V
• Subject: Analysis / Angiogenesis / Animals / Biology / Biomedical and Life Sciences / Biomedicine / blood supply / Bone Morphogenetic Protein 2 / Bone Morphogenetic Protein 2 - pharmacology / Cell Cycle / Cell Cycle - drug effects / Cell Movement / Cell Movement - drug effects / Cell Proliferation / Cell Proliferation - drug effects / Chickens / chorioallantoic membrane / Chorioallantoic Membrane - blood supply / Chorioallantoic Membrane - drug effects / Computer-aided manufacturing / cytology / drug effects / enzymology / Fibroblast Growth Factor 2 / Fibroblast Growth Factor 2 - pharmacology / fibroblasts / Growth factors / Human Genetics / Human Umbilical Vein Endothelial Cells / Human Umbilical Vein Endothelial Cells - cytology / Human Umbilical Vein Endothelial Cells - drug effects / Human Umbilical Vein Endothelial Cells - enzymology / Human Umbilical Vein Endothelial Cells - physiology / Humans / Matrix Metalloproteinase 2 / Matrix Metalloproteinase 2 - metabolism / metabolism / Molecular Medicine / Neovascularization, Physiologic / Neovascularization, Physiologic - drug effects / pharmacology / physiology / Proteins / Proteomics / Regular Article / synergism / Time Factors / tissue engineering / Vascular endothelial growth factor / Vascular Endothelial Growth Factor A / Vascular Endothelial Growth Factor A - pharmacology / vascular endothelial growth factors