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Robust and Scalable Angiogenesis Assay of Perfused 3D Human iPSC-Derived Endothelium for Anti-Angiogenic Drug Screening. | LitMetric

Robust and Scalable Angiogenesis Assay of Perfused 3D Human iPSC-Derived Endothelium for Anti-Angiogenic Drug Screening.

Int J Mol Sci

Einthoven Laboratory for Vascular and Regenerative Medicine, Department of Internal Medicine (Nephrology), Leiden University Medical Center, 2333ZA Leiden, The Netherlands.

Published: July 2020

AI Article Synopsis

  • * The assay was tested for its effectiveness in screening anti-angiogenic drugs, revealing that iPSC-derived endothelial cells perform similarly to primary cells in key angiogenic processes like sprouting and lumen formation.
  • * Results show that the assay is reliable for drug screening, as it demonstrated significant inhibition of sprouting with known inhibitors, and met performance criteria for robust screening applications.

Article Abstract

To advance pre-clinical vascular drug research, assays are needed that closely mimic the process of angiogenesis . Such assays should combine physiological relevant culture conditions with robustness and scalability to enable drug screening. We developed a perfused 3D angiogenesis assay that includes endothelial cells (ECs) from induced pluripotent stem cells (iPSC) and assessed its performance and suitability for anti-angiogenic drug screening. Angiogenic sprouting was compared with primary ECs and showed that the microvessels from iPSC-EC exhibit similar sprouting behavior, including tip cell formation, directional sprouting and lumen formation. Inhibition with sunitinib, a clinically used vascular endothelial growth factor (VEGF) receptor type 2 inhibitor, and 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO), a transient glycolysis inhibitor, both significantly reduced the sprouting of both iPSC-ECs and primary ECs, supporting that both cell types show VEGF gradient-driven angiogenic sprouting. The assay performance was quantified for sunitinib, yielding a minimal signal window of 11 and Z-factor of at least 0.75, both meeting the criteria to be used as screening assay. In conclusion, we have developed a robust and scalable assay that includes physiological relevant culture conditions and is amenable to screening of anti-angiogenic compounds.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7370283PMC
http://dx.doi.org/10.3390/ijms21134804DOI Listing

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