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Combination of three angiogenic growth factors has synergistic effects on sprouting of endothelial cell/mesenchymal stem cell-based spheroids in a 3D matrix

Authors
Kim, Sook KyoungLee, JaeyeonSong, MyeongjinKim, MirimHwang, Soon JungJang, HwanseokPark, Yongdoo
Issue Date
11월-2016
Publisher
WILEY
Keywords
angiogenesis/neovasculization; growth factor; matrix
Citation
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS, v.104, no.8, pp.1535 - 1543
Indexed
SCIE
SCOPUS
Journal Title
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS
Volume
104
Number
8
Start Page
1535
End Page
1543
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/87019
DOI
10.1002/jbm.b.33498
ISSN
1552-4973
Abstract
Combinations of angiogenic growth factors have been shown to have synergistic effects on angiogenesis and natural wound healing in various animal models. Each growth factor has unique roles during angiogenesis; vascular endothelial growth factor (VEGF) plays a key role during the initial step of angiogenesis, whereas PDGF functions in the maturation of blood vessels. We used a combination of three angiogenic growth factors to increase angiogenesis in vitro and in vivo. We chose VEGF as a basic factor and added platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) to induce angiogenesis in three in vitro and in vivo models: 3D angiogenesis assay, 3D co-culture, and matrigel plug implantation assay. Cell proliferation was significantly higher in co-cultured cells treated with PDGF + VEGF + FGF than in the control, single, or dual combination groups. mRNA expression of a-smooth muscle actin (alpha-SMA), von Willebrand factor (vWF), and CD105 was higher in the triple group (PDGF + VEGF + FGF) than in control, single, or dual combination groups. In the PDGF + VEGF + FGF group, the length and number of branches of spheroids was also significantly higher than in the control, single, or dual combination groups. Furthermore, in a nude mouse model, a-SMA expression was significantly higher in the PDGF + VEGF + FGF group than in other groups. In conclusion, the addition of PDGF and FGF to VEGF showed synergistic effects on angiogenesis in vitro and in vivo. (C) 2015 Wiley Periodicals, Inc.
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