Pleural Effusion Aspirate for Use in 3D Lung Cancer Modeling and Chemotherapy Screening
Open accessAbstract
Lung cancer is the leading cause of cancer-related death worldwide, yet in vitro disease models have been limited to traditional 2D culture utilizing cancer cell lines. In contrast, recently developed 3D models (organoids) have been adopted by researchers to improve the physiological relevance of laboratory study. We have hypothesized that 3D hydrogel-based models will allow for improved disease replication and characterization over standard 2D culture using cells taken directly from patients. Here, we have leveraged the use of 3D hydrogel-based models to create lung cancer organoids using a unique cell source, pleural effusion aspirate, from multiple lung cancer patients. With these 3D models, we have characterized the cell populations comprising the pleural effusion aspirate and have tracked phenotypic changes that develop during short-term in vitro culture. We found that isolated, patient cells placed directly into organoids created anatomically relevant structures and exhibited lung-cancer-specific behaviors. On the other hand, cells first grown in plastic dishes and then cultured in 3D did not create similar structures. Further, we have been able to compare chemotherapeutic response of patient cells between 2D and 3D cell culture systems. Our results show that cells in 2D culture were more sensitive to treatment when compared with 3D organoids. Collectively, we have been able to utilize tumor cells from pleural effusion fluid of lung cancer patients to create organoids that display in-vivo- like anatomy and drug response and thus could serve as more accurate disease models for study of tumor progression and drug development.
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Tumor cells from liquid samples such as peripheral blood, ascites, and pleural effusions can be used as starting material to generate organoids.
“Tumor cells isolated from liquid samples such as peripheral blood52, ascites50,53, and pleural effusions54 can also be used as starting material to generate organoids.”
From Organoids (2022) · cites this paper as [53]
Invasiveness of tumor cells was enhanced in the presence of spontaneously formed vasculature.
“the invasiveness of tumor cells was enhanced in the presence of spontaneously formed vasculature.”
From 3D Biomimetic Models to Reconstitute Tumor Microenvironment In Vitro: Spheroids, Organoids, and Tumor‐on‐a‐Chip (2023) · cites this paper as [120]
The Results describe tumor-cell and fibroblast outgrowth in organoids, and the Discussion describes branching structures supported by stromal cells. Neither passage reports spontaneously formed vasculature or tests whether its presence enhances tumor-cell invasiveness (searched: vasculature, vascular cells, invasion, angiogenesis). (LLM, conf=0.75)
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Self-citationPromising preclinical models for lung cancer research—lung cancer organoids: a narrative review
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A Two-Step Protocol for Isolation and Maintenance of Lung Cancer Primary 3D Cultures
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Skardal, A., Sivakumar, H., Rodríguez, M., Popova, L. V., & Dedhia, P. H. (2024) · Endocrine Related Cancer · doi:10.1530/erc-23-0344 · Cited by 4 · see citing works
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Tissue organoid models and applications
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Additive Manufacturing of Smart Bionanomaterials for Fabrication of Medical Implants
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Self-citation
- Authors
- Mazzocchi, A., Devarasetty, M., Herberg, S., Petty, W. J., Marini, F., Miller, L., Kucera, G., Dukes, D. K., Ruiz, J., Skardal, A., & Soker, S.
- Affiliations
- Virginia Tech - Wake Forest University School of Biomedical Engineering & Sciences (US)
- Wake Forest University Health Sciences (US)
- Atrium Health Wake Forest Baptist (US)
- Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, 391 Technology Way, Winston-Salem, North Carolina 27101, United States
- ORCID
- Venue
- ACS Biomaterials Science & Engineering
- Publisher
- American Chemical Society (ACS)
- Published
- 2019-03-08
- Volume
- 5
- Issue
- 4
- Pages
- 1937-1943
- ISSN
- 2373-9878 (ISSN-L)
- PMC
- PMC6853614
- OpenAlex
- W2921648992
- Cited by
- 82
- References
- 32
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 11 · 2023: 17 · 2022: 21 · 2021: 10 · 2020: 5 · 2019: 4
- FWCI
- 3.52
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- ACS Biomaterials Science & Engineering (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (5R33CA202822, P30CA012197)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
- Keywords
- lung cancer, lung cancer organoids, patient-derived tumor cells, chemotherapy response, 2D vs 3D cell culture, tumor progression, drug development
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