September 19, 2022
Interstitial fluid flow in the brain tumor microenvironment
Jenny Munson, PhD
Associate Professor, Fralin Biomedical Research Institute
Department of Biomedical Engineering & Mechanics
Fluid flow in the brain is an emerging area of research with implications in Alzheimer’s, aging, brain homeostasis, development, and cancer. In cancers, fluid flow is increased as pressure builds as tumors grow. In my laboratory, we study the role of interstitial fluid flow, or the fluid flow within the spaces of tissues, on cellular behaviors. We have developed an array of techniques and tools to measure, model, and manipulate fluid flow in the brain. In glioblastoma, the deadliest form of brain cancer, cellular invasion is a defining factor of its resistance to therapeutic intervention and poor patient prognosis. Invasion in the brain follows distinctive routes that correlate with interstitial and bulk flow pathways. To examine how interstitial fluid flow interacts with this specific invasive microenvironment, we have developed tissue engineered models of the brain that recapitulate patient tissue. We have found that interstitial flow can enhance invasion of brain cancer cells, mediated simultaneously by chemical and mechanical mechanisms. In order to better understand the nature of interstitial flow and its potential for prognosis and therapeutic intervention, we have developed MR imaging methods and analyses to map fluid flow routes in and around brain tumors. In this talk, I will discuss the nature and implications of interstitial fluid flow in the brain, identifying both tissue-level and cellular-level mechanisms and how our lab uses diverse approaches (in vitro, in vivo, ex vivo, in silico) to study this phenomenon.