Spatial control of oxygen delivery to 3D cultures alters cancer cell growth and gene expression

Wulftange, W. W.; Rose, M. A.; Garmendia-Cedillos, M.; da Silva, D.; Poprawski, J. E.; Srinivasachar, D.; Sullivan, T.; Lim, L.; Bliskovsky, V. V.; Hall, M. D.; Pohida, T. J.; Robey, R. W.; Morgan, N. Y.; Gottesman, M.

doi:10.1101/522656

bioRxiv · 10.1101/522656

Spatial control of oxygen delivery to 3D cultures alters cancer cell growth and gene expression

Wulftange, W. W.·Rose, M. A.·Garmendia-Cedillos, M.·da Silva, D.·Poprawski, J. E.·Srinivasachar, D.·Sullivan, T.·Lim, L.·Bliskovsky, V. V.·Hall, M. D.·Pohida, T. J.·Robey, R. W.·Morgan, N. Y.·Gottesman, M.

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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 bioreactor system where cancer cells are grown in Matrigel in modified 6-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% to 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 2D monolayer culture and 3D Matrigel culture in 21% oxygen. We conclude that controlled oxygen delivery may provide a more physiologically relevant 3D system.

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Wulftange, W. W., Rose, M. A., Garmendia-Cedillos, M., da Silva, D., Poprawski, J. E., Srinivasachar, D., Sullivan, T., Lim, L., Bliskovsky, V. V., Hall, M. D., Pohida, T. J., Robey, R. W., Morgan, N. Y., Gottesman, M.. 2019-01-17. Spatial control of oxygen delivery to 3D cultures alters cancer cell growth and gene expression. https://doi.org/10.1101/522656

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