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Reprod Toxicol. 2017 Jun;70:116-125. doi: 10.1016/j.reprotox.2016.11.015. Epub 2016 Nov 30.

Intra-laboratory validated human cell-based in vitro vasculogenesis/angiogenesis test with serum-free medium.

Author information

1
FICAM, University of Tampere, Finland. Electronic address: tarja.toimela@staff.uta.fi.
2
FICAM, University of Tampere, Finland.
3
Cell Biology, University of Tampere, Finland; Science Center, Tampere University Hospital, Finland.

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.

KEYWORDS:

Angiogenesis; Chemical testing; Human adipose stromal cells; Human umbilical cord vein endothelial cells; In vitro; Teratogens; Vasculogenesis

PMID:
27915012
DOI:
10.1016/j.reprotox.2016.11.015
[Indexed for MEDLINE]

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