Three Dimensional Microfluidic Cell Arrays for ex Vivo Drug Screening with Mimicked Vascular Flow
Open accessAbstract
Currently, there are no reliable ex vivo models that predict anticancer drug responses in human tumors accurately. A comprehensive method of mimicking a 3D microenvironment to study effects of anticancer drugs on specific cancer types is essential. Here, we report the development of a three-dimensional microfluidic cell array (3D μFCA), which reconstructs a 3D tumor microenvironment with cancer cells and microvascular endothelial cells. To mimic the in vivo spatial relationship between microvessels and nonendothelial cells embedded in extracellular matrix, three polydimethylsiloxane (PDMS) layers were built into this array. The multilayer property of the device enabled the imitation of the drug delivery in a microtissue array with simulated blood circulation. This 3D μFCA system may provide better predictions of drug responses and identification of a suitable treatment for a specific patient if biopsy samples are used. To the pharmaceutical industry, the scaling-up of our 3D μFCA system may offer a novel high throughput screening tool.
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Current microfluidic tumor models with mimicked vasculature have demonstrated that tumor cells exhibit increased drug resistance when artificial blood vessels were used.
“Current microfluidic tumor models with mimicked vasculature have demonstrated that tumor cells exhibit increased drug resistance when artificial blood vessels were used [81].”
From Microfluidic modelling of the tumor microenvironment for anti-cancer drug development (2019) · cites this paper as [81]
The Results (Profiles of Caspase-3 Activity in Different Culture Configurations; page unavailable) report slower and lower maximum drug responses in PC9 lung cancer cells cultured with mimicked microvessels than in static 3D coculture. This supports reduced drug response in that comparison, but the broader claim of increased tumor-cell drug resistance overstates the finding: the authors measured apoptotic response and only speculate that the endothelial layer delayed drug delivery. (LLM, conf=0.84)
Experimental — accuracy not yet measuredIn a device with an HMVEC monolayer on a porous PDMS layer, human non-small cell lung cancer PC9 cells had stronger drug resistance to four different apoptotic inducers than two-dimensional cultured PC9 cells.
“It was shown that human non-small cell lung cancer cells (PC9) cultured in their devices had stronger drug resistance to four different apoptotic inducers than two-dimensional cultured PC9 cells.”
From Microfluidic modelling of the tumor microenvironment for anti-cancer drug development (2019) · cites this paper as [81]
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- Authors
- Dereli-Korkut, Z., Akaydin, H. D., Ahmed, A. H. R., Jiang, X., & Wang, S.
- Affiliations
- The City College of the City University of New York , , 160 Convent Ave. Steinman Hall T-434 , , ,
- Stanford University (US)
- City College of New York (US)
- Memorial Sloan Kettering Cancer Center (US)
- Corresponding author
- Wang, Sihong
- Venue
- Analytical Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2014-02-25
- Volume
- 86
- Issue
- 6
- Pages
- 2997-3004
- ISSN
- 0003-2700 (ISSN-L)
- 1520-6882
- PMC
- PMC3982971
- OpenAlex
- W2319017750
- Semantic Scholar
- a126e0ab4fc49d446dae1ad3a9b3a0745b352672
- Cited by
- 62
- References
- 48
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 5 · 2023: 5 · 2022: 7 · 2021: 6 · 2020: 4 · 2019: 11 · 2018: 3 · 2017: 5 · 2016: 7 · 2015: 4 · 2014: 1
- FWCI
- 2.94
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Analytical Chemistry (publishedVersion, other-oa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- CUNY Academic Works (City University of New York) (submittedVersion)
- Funders
- National Science Foundation
- National Institutes of Health
- National Cancer Institute (U54CA137788)
- Division of Chemical, Bioengineering, Environmental, and Transport Systems
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Physical Sciences › Engineering › Biomedical Engineering › Microfluidic and Capillary Electrophoresis Applications
- Physical Sciences › Engineering › Biomedical Engineering › Microfluidic and Bio-sensing Technologies
- Keywords
- ex vivo drug testing, anticancer drug response, tumor microenvironment, microvascular endothelial cells, microvascular blood flow, extracellular matrix, high-throughput screening, precision oncology
- MeSH terms
- Antineoplastic Agents, Drug Screening Assays, Antitumor, Humans, Microscopy, Electron, Scanning, Molecular Mimicry, Microfluidics, Cell Line, Tumor, Tumor Microenvironment
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