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J Cell Physiol. 2019 Nov;234(11):20608-20622. doi: 10.1002/jcp.28665. Epub 2019 Apr 22.

Spatial control of oxygen delivery to three-dimensional cultures alters cancer cell growth and gene expression.

Author information

1
Trans-NIH Shared Resources on Biomedical Engineering and Physical Sciences (BEPS), National Institutes of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health, Bethesda, Maryland.
2
Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
3
Division of Computational Bioscience, Center for Information Technology, National Institutes of Health, Bethesda, Maryland.
4
Confocal Microscopy Core Facility, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
5
CCR Genomics Core, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
6
National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, Maryland.

Abstract

Commonly used monolayer cancer cell cultures fail to provide a physiologically relevant environment in terms of oxygen delivery. Here, we describe a three-dimensional (3D) bioreactor system where cancer cells are grown in Matrigel in modified six-well plates. Oxygen is delivered to the cultures through a polydimethylsiloxane (PDMS) membrane at the bottom of the wells, with microfabricated PDMS pillars to control oxygen delivery. The plates receive 3% oxygen from below and 0% oxygen at the top surface of the media, providing a gradient of 3-0% oxygen. We compared growth and transcriptional profiles for cancer cells grown in Matrigel in the bioreactor, 3D cultures grown in 21% oxygen, and cells grown in a standard hypoxia chamber at 3% oxygen. Additionally, we compared gene expression of conventional two-dimensional monolayer culture and 3D Matrigel culture in 21% oxygen. We conclude that controlled oxygen delivery may provide a more physiologically relevant 3D system.

KEYWORDS:

3D cell culture; RNA-seq; bioreactor; capillary oxygenation; oxygen gradient; transcriptome; tumor microenvironment

PMID:
31012116
PMCID:
PMC6660365
[Available on 2020-11-01]
DOI:
10.1002/jcp.28665

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