Towards personalized medicine with a three-dimensional micro-scale perfusion-based two-chamber tissue model system
Open accessAbstract
A three-dimensional micro-scale perfusion-based two-chamber (3D-μPTC) tissue model system was developed to test the cytotoxicity of anticancer drugs in conjunction with liver metabolism. Liver cells with different cytochrome P450 (CYP) subtypes and glioblastoma multiforme (GBM) brain cancer cells were cultured in two separate chambers connected in tandem. Both chambers contained a 3D tissue engineering scaffold fabricated with biodegradable poly(lactic acid) (PLA) using a solvent-free approach. We used this model system to test the cytotoxicity of anticancer drugs, including temozolomide (TMZ) and ifosfamide (IFO). With the liver cells, TMZ showed a much lower toxicity to GBM cells under both 2D and 3D cell culture conditions. Comparing 2D, GBM cells cultured in 3D had much high viability under TMZ treatment. IFO was used to test the CYP-related metabolic effects. Cells with different expression levels of CYP3A4 differed dramatically in their ability to activate IFO, which led to strong metabolism-dependent cytotoxicity to GBM cells. These results demonstrate that our 3D-μPTC system could provide a more physiologically realistic in vitro environment than the current 2D monolayers for testing metabolism-dependent toxicity of anticancer drugs. It could therefore be used as an important platform for better prediction of drug dosing and schedule towards personalized medicine.
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Ma et al. established a two-chamber (3D-mPTC) tissue model based on three-dimensional microscale perfusion, combined with cytotoxicity of liver metabolism anticancer drugs for detection.
“Ma et al. established a two-chamber (3D-mPTC) tissue model based on three-dimensional microscale perfusion in early research, which was combined with the cytotoxicity of liver metabolism anticancer drugs for detection, and realized the most basic organ chip model (Fig. 7b)219.”
From Tumor-on-a-chip: from bioinspired design to biomedical application (2021) · cites this paper as [219]
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Self-citation
- Authors
- Ma, L., Barker, J., Zhou, C., Li, W., Zhang, J., Lin, B., Foltz, G., Küblbeck, J., & Honkakoski, P.
- Affiliations
- University of Washington (US)
- The University of Texas at Austin (US)
- Swedish Medical Center (US)
- University of Eastern Finland (FI)
- Corresponding author
- Li, Wei
- Lin, Biaoyang
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2012-06
- Volume
- 33
- Issue
- 17
- Pages
- 4353-4361
- ISSN
- 0142-9612 (ISSN-L)
- PMC
- PMC3569495
- OpenAlex
- W2064252921
- Cited by
- 83
- References
- 69
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 4 · 2023: 2 · 2022: 8 · 2021: 7 · 2020: 7 · 2019: 8 · 2018: 8 · 2017: 6 · 2016: 9 · 2015: 6 · 2014: 7 · 2013: 4 · 2012: 1
- FWCI
- 3.28
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Biomaterials (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (R21EB008573)
- NSF (CMMI-0348767, CMMI-1131710)
- University of Eastern Finland
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
- Keywords
- personalized medicine, anticancer drug cytotoxicity, drug metabolism, cytochrome P450, CYP3A4, glioblastoma, temozolomide, ifosfamide, 3D cell culture, polylactic acid scaffolds, drug toxicity prediction
- MeSH terms
- Temozolomide, Cell Survival, Dacarbazine, Glioblastoma, Humans, Ifosfamide, Liver, Microscopy, Electron, Scanning, Perfusion, Polyesters, Diffusion Chambers, Culture, Porosity, Cell Culture Techniques, Tissue Engineering, Cell Line, Tumor, Cytochrome P-450 CYP3A, Tissue Scaffolds, Precision Medicine
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