title: Hypoxia enhances angiogenesis in an adipose-derived stromal cell/endothelial cell co-culture 3D gel model.
abstract: OBJECTIVE
  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).
  
  
  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.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan Province, 610041, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan Province, 610041, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan Province, 610041, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Zhong
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan Province, 610041, China.
authors.forename: Xiangzhu
authors.initials: X
authors.lastname: Cun
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan Province, 610041, China.
authors.forename: Shiyu
authors.initials: S
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan Province, 610041, China.
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan Province, 610041, China.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Cai
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism; D018929:Cell Culture Techniques; D015687:Cell Hypoxia / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000378:metabolism*; D005260:Female; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D018919:Neovascularization, Physiologic / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D019485:Bone Morphogenetic Proteins; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse