Microfluidic platform for three-dimensional cell culture under spatiotemporal heterogeneity of oxygen tension
Cells in a tumor microenvironment are exposed to spatial and temporal variations in oxygen tension due to hyperproliferation and immature vascularization. Such spatiotemporal oxygen heterogeneity affects the behavior of cancer cells, leading to cancer growth and metastasis, and thus, it is essential...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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AIP Publishing LLC
2020-03-01
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| Series: | APL Bioengineering |
| Online Access: | http://dx.doi.org/10.1063/1.5127069 |
| _version_ | 1819064308615610368 |
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| author | Rei Koens Yugo Tabata Jean C. Serrano Satoshi Aratake Daisuke Yoshino Roger D. Kamm Kenichi Funamoto |
| author_facet | Rei Koens Yugo Tabata Jean C. Serrano Satoshi Aratake Daisuke Yoshino Roger D. Kamm Kenichi Funamoto |
| author_sort | Rei Koens |
| collection | DOAJ |
| description | Cells in a tumor microenvironment are exposed to spatial and temporal variations in oxygen tension due to hyperproliferation and immature vascularization. Such spatiotemporal oxygen heterogeneity affects the behavior of cancer cells, leading to cancer growth and metastasis, and thus, it is essential to clarify the cellular responses of cancer cells to oxygen tension. Herein, we describe a new double-layer microfluidic device allowing the control of oxygen tension and the behavior of cancer cells under spatiotemporal oxygen heterogeneity. Two parallel gas channels were located above the media and gel channels to enhance gas exchange, and a gas-impermeable polycarbonate film was embedded in the device to prevent the diffusion of atmospheric oxygen. Variations in oxygen tension in the device with the experimental parameters and design variables were investigated computationally and validated by using oxygen-sensitive nanoparticles. The present device can generate a uniform hypoxic condition at oxygen levels down to 0.3% O2, as well as a linear oxygen gradient from 3% O2 to 17% O2 across the gel channel within 15 min. Moreover, human breast cancer cells suspended in type I collagen gel were introduced in the gel channel to observe their response under controlled oxygen tension. Hypoxic exposure activated the proliferation and motility of the cells, which showed a local maximum increase at 5% O2. Under the oxygen gradient condition, the increase in the cell number was relatively high in the central mild hypoxia region. These findings demonstrate the utility of the present device to study cellular responses in an oxygen-controlled microenvironment. |
| first_indexed | 2024-12-21T15:28:30Z |
| format | Article |
| id | doaj.art-a16b86fcdbde40db87f1ad226850c991 |
| institution | Directory Open Access Journal |
| issn | 2473-2877 |
| language | English |
| last_indexed | 2024-12-21T15:28:30Z |
| publishDate | 2020-03-01 |
| publisher | AIP Publishing LLC |
| record_format | Article |
| series | APL Bioengineering |
| spelling | doaj.art-a16b86fcdbde40db87f1ad226850c9912022-12-21T18:58:51ZengAIP Publishing LLCAPL Bioengineering2473-28772020-03-0141016106016106-1110.1063/1.5127069Microfluidic platform for three-dimensional cell culture under spatiotemporal heterogeneity of oxygen tensionRei Koens0Yugo Tabata1Jean C. Serrano2Satoshi Aratake3Daisuke Yoshino4Roger D. Kamm5Kenichi Funamoto6 Graduate School of Biomedical Engineering, Tohoku University, 6-6-12 Aramaki-aza Aoba, Aoba-ku, Sendai, Miyagi 980-8579, Japan Graduate School of Biomedical Engineering, Tohoku University, 6-6-12 Aramaki-aza Aoba, Aoba-ku, Sendai, Miyagi 980-8579, Japan Department of Mechanical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Ave., Cambridge, Massachusetts 02139, USA Institute of Fluid Science, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai, Miyagi 980-8577, Japan Frontier Research Institute for Interdisciplinary Sciences, Tohoku University, 6-3 Aramaki-aza Aoba, Aoba-ku, Sendai, Miyagi 980-8578, Japan Department of Mechanical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Ave., Cambridge, Massachusetts 02139, USA Institute of Fluid Science, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai, Miyagi 980-8577, JapanCells in a tumor microenvironment are exposed to spatial and temporal variations in oxygen tension due to hyperproliferation and immature vascularization. Such spatiotemporal oxygen heterogeneity affects the behavior of cancer cells, leading to cancer growth and metastasis, and thus, it is essential to clarify the cellular responses of cancer cells to oxygen tension. Herein, we describe a new double-layer microfluidic device allowing the control of oxygen tension and the behavior of cancer cells under spatiotemporal oxygen heterogeneity. Two parallel gas channels were located above the media and gel channels to enhance gas exchange, and a gas-impermeable polycarbonate film was embedded in the device to prevent the diffusion of atmospheric oxygen. Variations in oxygen tension in the device with the experimental parameters and design variables were investigated computationally and validated by using oxygen-sensitive nanoparticles. The present device can generate a uniform hypoxic condition at oxygen levels down to 0.3% O2, as well as a linear oxygen gradient from 3% O2 to 17% O2 across the gel channel within 15 min. Moreover, human breast cancer cells suspended in type I collagen gel were introduced in the gel channel to observe their response under controlled oxygen tension. Hypoxic exposure activated the proliferation and motility of the cells, which showed a local maximum increase at 5% O2. Under the oxygen gradient condition, the increase in the cell number was relatively high in the central mild hypoxia region. These findings demonstrate the utility of the present device to study cellular responses in an oxygen-controlled microenvironment.http://dx.doi.org/10.1063/1.5127069 |
| spellingShingle | Rei Koens Yugo Tabata Jean C. Serrano Satoshi Aratake Daisuke Yoshino Roger D. Kamm Kenichi Funamoto Microfluidic platform for three-dimensional cell culture under spatiotemporal heterogeneity of oxygen tension APL Bioengineering |
| title | Microfluidic platform for three-dimensional cell culture under spatiotemporal heterogeneity of oxygen tension |
| title_full | Microfluidic platform for three-dimensional cell culture under spatiotemporal heterogeneity of oxygen tension |
| title_fullStr | Microfluidic platform for three-dimensional cell culture under spatiotemporal heterogeneity of oxygen tension |
| title_full_unstemmed | Microfluidic platform for three-dimensional cell culture under spatiotemporal heterogeneity of oxygen tension |
| title_short | Microfluidic platform for three-dimensional cell culture under spatiotemporal heterogeneity of oxygen tension |
| title_sort | microfluidic platform for three dimensional cell culture under spatiotemporal heterogeneity of oxygen tension |
| url | http://dx.doi.org/10.1063/1.5127069 |
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