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DOI: 10.3791/66604-v
Samantha Howerton1,2, Yanping Liang1, Jennifer Hammel1,3, Benjamin Purow4, Jennifer Munson1,3
1Fralin Biomedical Research Institute at Virginia Tech Carilion, 2Translational Biology, Medicine, and Health Graduate Program,Virginia Tech, 3Department of Biomedical Engineering & Mechanics,Virginia Tech, 4Department of Neurology,University of Virginia School of Medicine
We present a method for replicating the glioma tumor microenvironment at the invasive front that incorporates interstitial fluid flow. This model is a hyaluronan-collagen I hydrogel in a tissue culture insert where a fluid pressure head can be applied. Invasion can be quantified, and cells can be isolated or lysed.
Our work investigates how the tumor microenvironment drives invasion of tumor cells in glioblastoma, the deadliest form of brain cancer. Specifically, we're interested in how interstitial fluid flow driven by increased intratumoral pressures causes tumor cells to invade into the surrounding brain parenchyma. We currently use the 3D hyaluronic acid collagen system mass models, combined with MRI imaging and a computational analysis to study glioma invasion driven by interstitial fluid flow.
For the in vitro approaches, fluid flow is generated by applying pressure on the top of the TME model, mimicking interstitial fluid flow in the brain. Providing the right physical cues to replicate the tissue microenvironment is a continual challenge. Our three dimensional model uses hyaluronic acid and collagen, both found in the brain matrix, and sustained interstitial fluid flow.
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