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Article

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

1
Einthoven Laboratory for Vascular and Regenerative Medicine, Department of Internal Medicine (Nephrology), Leiden University Medical Center, 2333ZA Leiden, The Netherlands
2
Department of Analytical BioSciences and Metabolomics, Division of Systems Biomedicine and Pharmacology, Leiden University, 2333CC Leiden, The Netherlands
3
Ncardia, 2333 BD Leiden, The Netherlands
4
Mimetas, 2333 CA Leiden, The Netherlands
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(13), 4804; https://doi.org/10.3390/ijms21134804
Received: 12 May 2020 / Revised: 28 June 2020 / Accepted: 2 July 2020 / Published: 7 July 2020
(This article belongs to the Special Issue hiPSC-Derived Cells as Models for Drug Discovery)
To advance pre-clinical vascular drug research, in vitro assays are needed that closely mimic the process of angiogenesis in vivo. 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. View Full-Text
Keywords: angiogenesis; drug screening; microfluidics; iPSC; endothelial cells angiogenesis; drug screening; microfluidics; iPSC; endothelial cells
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MDPI and ACS Style

van Duinen, V.; Stam, W.; Mulder, E.; Famili, F.; Reijerkerk, A.; Vulto, P.; Hankemeier, T.; van Zonneveld, A.J. Robust and Scalable Angiogenesis Assay of Perfused 3D Human iPSC-Derived Endothelium for Anti-Angiogenic Drug Screening. Int. J. Mol. Sci. 2020, 21, 4804. https://doi.org/10.3390/ijms21134804

AMA Style

van Duinen V, Stam W, Mulder E, Famili F, Reijerkerk A, Vulto P, Hankemeier T, van Zonneveld AJ. Robust and Scalable Angiogenesis Assay of Perfused 3D Human iPSC-Derived Endothelium for Anti-Angiogenic Drug Screening. International Journal of Molecular Sciences. 2020; 21(13):4804. https://doi.org/10.3390/ijms21134804

Chicago/Turabian Style

van Duinen, Vincent, Wendy Stam, Eva Mulder, Farbod Famili, Arie Reijerkerk, Paul Vulto, Thomas Hankemeier, and Anton J. van Zonneveld. 2020. "Robust and Scalable Angiogenesis Assay of Perfused 3D Human iPSC-Derived Endothelium for Anti-Angiogenic Drug Screening" International Journal of Molecular Sciences 21, no. 13: 4804. https://doi.org/10.3390/ijms21134804

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