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2017 ; 7
(1
): 15233
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A Microdevice Platform Recapitulating Hypoxic Tumor Microenvironments
#MMPMID29123197
Ando Y
; Ta HP
; Yen DP
; Lee SS
; Raola S
; Shen K
Sci Rep
2017[Nov]; 7
(1
): 15233
PMID29123197
show ga
Hypoxia plays a central role in cancer progression and resistance to therapy. We
have engineered a microdevice platform to recapitulate the intratumor oxygen
gradients that drive the heterogeneous hypoxic landscapes in solid tumors. Our
design features a "tumor section"-like culture by incorporating a cell layer
between two diffusion barriers, where an oxygen gradient is established by
cellular metabolism and physical constraints. We confirmed the oxygen gradient by
numerical simulation and imaging-based oxygen sensor measurement. We also
demonstrated spatially-resolved hypoxic signaling in cancer cells through
immunostaining, gene expression assay, and hypoxia-targeted drug treatment. Our
platform can accurately generate and control oxygen gradients, eliminates complex
microfluidic handling, allows for incorporation of additional tumor components,
and is compatible with high-content imaging and high-throughput applications. It
is well suited for understanding hypoxia-mediated mechanisms in cancer disease
and other biological processes, and discovery of new therapeutics.
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