TRACER: a 3D engineered tumour for mapping cell metabolism and phenotype in heterogeneous microenvironments
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1
University of Toronto, Chemical Engineering and Applied Chemistry, Canada
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2
University of Cambridge, MRC Cancer Unit, United Kingdom
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3
Princess Margaret Cancer Center and Campbell Family Institute for Cancer Research, Medical Biophysics and Radiation Oncology, Canada
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4
Institute of Biomaterials and Biomedical Engineering, University of Toronto, Canada
In recent years, emphasis has been placed on developing in vitro platforms that recapitulate the native tissue microenvironment to enable more effective compound screening compared with 2D culture. Though many systems - especially cancer models - have been engineered with physiological complexity, rarely has emphasis been placed on modes of data collection – limiting their applications. Here we describe an engineered tumour developed with data retrieval in mind. The model is assembled through single step rolling of a scaffold-tumour cell composite strip into a layered 3D coil. The model can be rapidly disassembled by unrolling for snapshot data analysis of tumour microenvironment in sync with cell phenotype in each of the layers. The model mimics the region of tumour tissue adjacent to a blood vessel, and recapitulates growth variations, gene expression profiles, and therapy responses consistent with tumours in vivo. Using our model, we show that the establishment of oxygen gradients are shaped by oxygen dependant signalling pathways, and use liquid chromatography tandem mass spectrometry to map cellular metabolism in 3D, concomitant to oxygen gradient. Our analysis identifies spatially defined metabolic signatures of cancer, revealing both known and novel metabolic responses to hypoxia.
Keywords:
Tissue Engineering,
biomimetic culture,
complex tissue orgnization,
instructive microenvironment
Conference:
10th World Biomaterials Congress, Montréal, Canada, 17 May - 22 May, 2016.
Presentation Type:
Poster
Topic:
Biomaterials in constructing tissue substitutes
Citation:
Rodenhizer
D,
Gaude
E,
Cojocari
D,
Mahadevan
R,
Frezza
C,
Wouters
BG and
Mcguigan
AP
(2016). TRACER: a 3D engineered tumour for mapping cell metabolism and phenotype in heterogeneous microenvironments.
Front. Bioeng. Biotechnol.
Conference Abstract:
10th World Biomaterials Congress.
doi: 10.3389/conf.FBIOE.2016.01.00859
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Received:
27 Mar 2016;
Published Online:
30 Mar 2016.