(276a) Microfluidic Hydrogel Cultures for Analysis of Oxygen-Dependent Angiogenic Signaling by Tumor Cells
AIChE Annual Meeting
2008
2008 Annual Meeting
Materials Engineering and Sciences Division
Cell-Material Interactions
Tuesday, November 18, 2008 - 2:35pm to 2:55pm
Tumors
consist of spatially and functionally distinct niches which may result from
spatiotemporal variation in oxygen concentration (pO2) within
growing tumors. Cells located in the periphery of tumors are well
nourished by diffusion of oxygen and nutrients from adjacent blood vessels (up
to ~ 200 mm), whereas cells located in the center of the tumors are exposed to
varying levels of hypoxia. We have recently shown that up-regulation of certain
angiogenic factors (e.g. vascular endothelial growth factor) is likely due to
low pO2 in central hypoxic niches, whereas other angiogenic factors
(e.g., interleukin-8) are only partially controlled by this aspect.
However, further investigation with spatiotemporal control of pO2 in
tissues is required to more explicitly clarify the role of pO2 in
angiogenic factor secretion. In this study, we have designed and explored
microfluidic tumor models to recreate and analyze distinct tumor niches by varying
pO2. Microchannels were embedded within alginate-based 3-D tumor
models to allow for spatiotemporal control of pO2 and subsequent
analysis of angiogenic factor secretion. Our strategy includes: 1) mathematical
modeling and experimental approaches to establish design requirements for
microfluidic tumors, 2) a lithographic technique to build functional microfluidic
structures within alginate hydrogels seeded with OSCC-3 (oral squamous
carcinoma cells), 3) confirmation of our ability to control pO2 with
oxygen-sensing microbeads, and 4) characterization of angiogenic factor
secretion as a function of spatiotemporal variations in pO2.
consist of spatially and functionally distinct niches which may result from
spatiotemporal variation in oxygen concentration (pO2) within
growing tumors. Cells located in the periphery of tumors are well
nourished by diffusion of oxygen and nutrients from adjacent blood vessels (up
to ~ 200 mm), whereas cells located in the center of the tumors are exposed to
varying levels of hypoxia. We have recently shown that up-regulation of certain
angiogenic factors (e.g. vascular endothelial growth factor) is likely due to
low pO2 in central hypoxic niches, whereas other angiogenic factors
(e.g., interleukin-8) are only partially controlled by this aspect.
However, further investigation with spatiotemporal control of pO2 in
tissues is required to more explicitly clarify the role of pO2 in
angiogenic factor secretion. In this study, we have designed and explored
microfluidic tumor models to recreate and analyze distinct tumor niches by varying
pO2. Microchannels were embedded within alginate-based 3-D tumor
models to allow for spatiotemporal control of pO2 and subsequent
analysis of angiogenic factor secretion. Our strategy includes: 1) mathematical
modeling and experimental approaches to establish design requirements for
microfluidic tumors, 2) a lithographic technique to build functional microfluidic
structures within alginate hydrogels seeded with OSCC-3 (oral squamous
carcinoma cells), 3) confirmation of our ability to control pO2 with
oxygen-sensing microbeads, and 4) characterization of angiogenic factor
secretion as a function of spatiotemporal variations in pO2.