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Robust and Scalable Angiogenesis Assay of Perfused 3D Human iPSC-Derived Endothelium for Anti-Angiogenic Drug Screening
- Source :
- International Journal of Molecular Sciences, Volume 21, Issue 13, International Journal of Molecular Sciences, 21(13). MDPI, International Journal of Molecular Sciences, 21(13), 4804. MDPI, International Journal of Molecular Sciences, Vol 21, Iss 4804, p 4804 (2020)
- Publication Year :
- 2020
- Publisher :
- Multidisciplinary Digital Publishing Institute, 2020.
-
Abstract
- 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.
- Subjects :
- Vascular Endothelial Growth Factor A
0301 basic medicine
Angiogenesis
Cell Culture Techniques
Drug Evaluation, Preclinical
Angiogenesis Inhibitors
02 engineering and technology
lcsh:Chemistry
chemistry.chemical_compound
angiogenesis
Induced pluripotent stem cell
lcsh:QH301-705.5
Cells, Cultured
Spectroscopy
iPSC
Neovascularization, Pathologic
Sunitinib
Chemistry
In vitro toxicology
Cell Differentiation
General Medicine
021001 nanoscience & nanotechnology
endothelial cells
Computer Science Applications
Vascular endothelial growth factor
medicine.anatomical_structure
Biological Assay
0210 nano-technology
medicine.drug
Cell type
Endothelium
Induced Pluripotent Stem Cells
microfluidics
Neovascularization, Physiologic
Article
Catalysis
Inorganic Chemistry
03 medical and health sciences
In vivo
Human Umbilical Vein Endothelial Cells
medicine
Humans
drug screening
Physical and Theoretical Chemistry
Molecular Biology
Organic Chemistry
030104 developmental biology
lcsh:Biology (General)
lcsh:QD1-999
Microvessels
Cancer research
Subjects
Details
- Language :
- English
- ISSN :
- 14220067
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences
- Accession number :
- edsair.doi.dedup.....9c5dd3b499b1c1d009ce813c0bee261c
- Full Text :
- https://doi.org/10.3390/ijms21134804