title: Intra-laboratory validated human cell-based in vitro vasculogenesis/angiogenesis test with serum-free medium.
abstract: Vasculogenesis and angiogenesis are the processes by which new blood vessels are formed. We have developed a serum-free human adipose stromal cell and umbilical cord vein endothelial cell based vasculogenesis/angiogenesis test. In this study, the test was validated in our GLP laboratory following the OECD Guidance Document 34 [1] using erlotinib, acetylic salicylic acid, levamisole, 2-methoxyestradiol, anti-VEGF, methimazole, and D-mannitol to show its reproducibility, repeatability, and predictivity for humans. The results were obtained from immunostained tubule structures and cytotoxicity assessment. The performance of the test was evaluated using 26 suspected teratogens and non-teratogens. The positive predictive value was 71.4% and the negative predictive value was 50.0%, indicating that inhibition of vasculogenesis is a significant mechanism behind teratogenesis. In conclusion, this test has great potential to be a screening test for prioritization purposes of chemicals and to be a test in a battery to predict developmental hazards in a regulatory context.
authors.affiliation: FICAM, University of Tampere, Finland. Electronic address: tarja.toimela@staff.uta.fi.
authors.forename: T
authors.initials: T
authors.lastname: Toimela
authors.affiliation: FICAM, University of Tampere, Finland.
authors.forename: O
authors.initials: O
authors.lastname: Huttala
authors.affiliation: FICAM, University of Tampere, Finland.
authors.forename: E
authors.initials: E
authors.lastname: Sabell
authors.affiliation: FICAM, University of Tampere, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Mannerström
authors.affiliation: Cell Biology, University of Tampere, Finland; Science Center, Tampere University Hospital, Finland.
authors.forename: J R
authors.initials: JR
authors.lastname: Sarkanen
authors.affiliation: Cell Biology, University of Tampere, Finland; Science Center, Tampere University Hospital, Finland.
authors.forename: T
authors.initials: T
authors.lastname: Ylikomi
authors.affiliation: FICAM, University of Tampere, Finland.
authors.forename: T
authors.initials: T
authors.lastname: Heinonen
mesh_terms: D000077584:2-Methoxyestradiol; D000273:Adipose Tissue / Q000166:cytology; D001241:Aspirin / Q000494:pharmacology; D002478:Cells, Cultured; D003470:Culture Media; D064420:Drug-Related Side Effects and Adverse Reactions; D000069347:Erlotinib Hydrochloride / Q000494:pharmacology; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007753:Laboratories; D007978:Levamisole / Q000494:pharmacology; D008353:Mannitol / Q000494:pharmacology; D008713:Methimazole / Q000494:pharmacology; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D015203:Reproducibility of Results; D044967:Serum; D017154:Stromal Cells / Q000187:drug effects* / Q000502:physiology; D013723:Teratogens / Q000633:toxicity*; D018675:Toxicity Tests / Q000379:methods*; D014470:Umbilical Cord / Q000166:cytology; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
chemical_list: D003470:Culture Media; D013723:Teratogens; D042461:Vascular Endothelial Growth Factor A; D007978:Levamisole; D008353:Mannitol; D004958:Estradiol; D008713:Methimazole; D000077584:2-Methoxyestradiol; D000069347:Erlotinib Hydrochloride; D001241:Aspirin
keywords: Angiogenesis; Chemical testing; Human adipose stromal cells; Human umbilical cord vein endothelial cells; In vitro; Teratogens; Vasculogenesis