High-throughput 3-D cell-based proliferation and cytotoxicity assays for drug screening and bioprocess development
Abstract
We have designed, built and tested a three-dimensional (3-D) cell culture system on modified microplates for high-throughput, real-time, proliferation and cytotoxicity assays. In this 3-D culture system, cells expressing the enhanced green fluorescent protein (EGFP) were cultured in nonwoven polyethylene terephthalate (PET) fibrous scaffolds. Compared to 2-D cultures in conventional microplates, 3-D cultures gave more than 10-fold higher fluorescence signals with significantly increased signal-to-noise ratio (SNR), thus extending the application of conventional fluorescence microplate readers for online monitoring of culture fluorescence. The 3-D system was successfully used to demonstrate the effects of fetal bovine serum, fibronectin coating of PET fibers, and cytotoxicity of dexamethasone on recombinant murine embryonic stem D3 cells. The dosage effects of 5-fluorouracil and gemcitabine on high-density colon cancer HT-29 cells were also tested. These studies demonstrated that the 3-D culture microplate system with EGFP expressing cells can be used as a high-throughput system in drug discovery and bioprocess development.
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3D models can better replicate intrinsic physiological conditions and in vivo cellular responses to external stimuli compared to the 2D monolayer.
“Therefore, 3D models can better replicate intrinsic physiological conditions and in vivo cellular responses to external stimuli compared to the 2D monolayer. 77,78,80-82”
From Three-dimensional cell culture systems and their applications in drug discovery and cell-based biosensors (2014) · cites this paper as [82]
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- Authors
- Zhang, X., & Yang, S.-T.
- Affiliations
- The Ohio State University (US)
- Corresponding author
- Yang, Shang-Tian
- Venue
- Journal of Biotechnology
- Publisher
- Elsevier BV
- Published
- 2011-01
- Volume
- 151
- Issue
- 2
- Pages
- 186-193
- ISSN
- 0168-1656 (ISSN-L)
- OpenAlex
- W2021899559
- Cited by
- 43
- References
- 42
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 3 · 2022: 1 · 2021: 1 · 2019: 6 · 2018: 3 · 2017: 4 · 2016: 2 · 2015: 3 · 2014: 2 · 2013: 6 · 2012: 6
- FWCI
- 2.83
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Biotechnology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Keywords
- 3D cell culture, high-throughput screening, cell proliferation assay, cytotoxicity assay, enhanced green fluorescent protein, embryonic stem cells, colon cancer cells, 5-fluorouracil, gemcitabine, bioprocess development
- MeSH terms
- Animals, Biotechnology, Drug Industry, Drug Evaluation, Preclinical, Fibronectins, Humans, Image Processing, Computer-Assisted, Kinetics, Drug Design, Imaging, Three-Dimensional, Cell Line, Tumor, Cell Proliferation, Green Fluorescent Proteins, Mice, Embryonic Stem Cells
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