Vascularized cancer on a chip: the effect of perfusion on growth and drug delivery of tumor spheroid
Open accessAbstract
Tumor vasculature creates a hostile tumor microenvironment (TME) in vivo and nourishes cancers, resulting in cancer progression and drug resistance. To mimic the biochemical and biomechanical environments of tumors in vitro, several models integrated with a vascular network have been reported. However, the tumor responses to biochemical and biomechanical stimuli were evaluated under static conditions and failed to incorporate the effects of blood flow to tumors. In this study, we present a tumor-on-a-chip platform that enables the evaluation of tumor activities with intraluminal flow in an engineered tumor vascular network. The fibroblasts in the tumor spheroid induced angiogenic sprouts, which constructed a perfusable vascular network in a tumor spheroid. The perfusability of the engineered vascular network was preserved during the culture. Moreover, perfusion for over 24 h significantly increased the proliferation activities of tumor cells and decreased cell death in the spheroid. Drug administration under perfusion condition did not show the dose-dependent effects of anticancer drugs on tumor activities in contrast to the results under static conditions. Our results demonstrate the importance of flow in a vascular network for the evaluation of tumor activities in a drug screening platform.
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Vascularization of tumoroids can be maintained for 22 days.
“the vascularization of tumoroids can be maintained for 22 days.”
From 3D Biomimetic Models to Reconstitute Tumor Microenvironment In Vitro: Spheroids, Organoids, and Tumor‐on‐a‐Chip (2023) · cites this paper as [104]
Sprouting from the endothelial layer in the side channels into the middle compartment containing a tumor spheroid was triggered by the presence of fibroblasts in the spheroids.
“Sprouting from the endothelial layer in the side channels into the middle compartment containing a tumor spheroid was triggered by the presence of fibroblasts in the spheroids [58].”
From Cancer-on-chip models for metastasis: importance of the tumor microenvironment (2024) · cites this paper as [58]
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- Authors
- Nashimoto, Y., Okada, R., Hanada, S., Arima, Y., Nishiyama, K., Miura, T., & Yokokawa, R.
- Affiliations
- Tohoku University (JP)
- Kyoto University (JP)
- International Research Center for Medical Sciences, Kumamoto University (JP)
- Kyushu University (JP)
- Corresponding author
- Yokokawa, Ryuji
- ORCID
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2020-01
- Volume
- 229
- Pages
- 119547
- ISSN
- 0142-9612 (ISSN-L)
- OpenAlex
- W2981018318
- Cited by
- 332
- References
- 44
- Citations by year
- 2026: 36 · 2025: 46 · 2024: 66 · 2023: 59 · 2022: 58 · 2021: 39 · 2020: 28
- FWCI
- 10.97
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Biomaterials (acceptedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science
- Nakatomi Foundation
- Japan Science and Technology Agency
- Japan Agency for Medical Research and Development
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Physical Sciences › Mathematics › Modeling and Simulation › Mathematical Biology Tumor Growth
- Keywords
- tumor-on-a-chip, tumor spheroids, perfusion, tumor vasculature, fibroblasts, tumor microenvironment, tumor cell proliferation, cell death, anticancer drug delivery, drug screening, blood flow
- MeSH terms
- Pharmaceutical Preparations, Humans, Neoplasms, Perfusion, Lab-On-A-Chip Devices, Tumor Microenvironment
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