Hypoxia enhances angiogenesis in an adipose-derived stromal cell/endothelial cell co-culture 3D gel model.

Abstract

OBJECTIVES:

This study aimed to investigate the influence of hypoxia on angiogenesis in a 3D gel, with co-culturing adipose-derived stromal cells (ASCs) and endothelial cells (ECs).

MATERIALS AND METHODS:

ASCs from green fluorescent protein-labeled mice and ECs from red fluorescent protein-labeled mice were co-cultured in 3D collagen gels at 1:1 ratio, in normal and hypoxic oxygen conditions, and morphology of angiogenesis was observed using confocal laser scanning microscopy. To discover changes in growth factors between monoculture ASCs and ECs, transwell co-cultures of ASCs and ECs were applied. Semi-quantitative PCR was performed to explore mRNA expression of growth factors.

RESULTS:

Enhanced angiogenesis was observed in 3D gels implanted with 1:1 mixture of ASCs and ECs after 7 days hypoxia. Genes including VEGFA/B, EGF-1, HIF-1a, IGF-1, PDGF, TGF-β1 and BMP-2/4 in ECs, both monoculture and co-culture, were significantly enhanced after being cultured under hypoxia. In comparison, genes VEGFA/B, EGF-1, HIF-1a, TGF-β1 and BMP-2 in ASCs increased. In all, factors VEGFA/B, EGF-1, HIF-1a, TGF-β1 and BMP-2 increased in both ASCs and ECs after being cultured in hypoxia no matter whether as monoculture or co-culture.

CONCLUSIONS:

Co-culture of ASCs and ECs at 1:1 ratio in a 3D gel under hypoxia promoted angiogenesis. Those growth factors which were increased in both ASCs and ECs, indicate that VEGFA/B, EGF-1, HIF-1a, TGF-β1 and BMP-2 might be responsible for enhancement in angiogenesis triggered by hypoxia.

• Authors: Qiang Xie, Jing Xie, Juan Zhong, Xiangzhu Cun, Shiyu Lin, Yunfeng Lin, Xiaoxiao Cai
• Journal: Cell proliferation (Cell Prolif) Vol. 49 Issue 2 Pg. 236-45 (Apr 2016) ISSN: 1365-2184 [Electronic] England
• PMID: 26997164 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2016 John Wiley & Sons Ltd.

Chemical References

• Bone Morphogenetic Proteins
• Vascular Endothelial Growth Factor A
• vascular endothelial growth factor A, mouse

Topics

• Adipocytes (metabolism)
• Adipose Tissue (cytology)
• Animals
• Bone Morphogenetic Proteins (genetics, metabolism)
• Cell Culture Techniques
• Cell Hypoxia (physiology)
• Cells, Cultured
• Coculture Techniques
• Endothelial Cells (metabolism)
• Female
• Mesenchymal Stem Cells (metabolism)
• Mice
• Neovascularization, Physiologic (physiology)
• Vascular Endothelial Growth Factor A (genetics, metabolism)