A Microfluidic Blood Brain Barrier Model to Study the Influence of Glioblastoma Tumor Cells on BBB Function

The blood brain barrier (BBB) plays an essential role in regulating brain function by controlling the transport of nutrients and preventing toxins from moving from the rest of the body's circulation into the brain. Because it is more selective than most other endothelial barriers, many therapeutic candidates fail to cross the BBB, making it difficult to design novel drugs to treat many pathologies in the brain. In addition, BBB dysfunction is observed in many brain diseases including glioblastoma (GB), an aggressive, universally fatal primary brain tumor. Here, a novel 3D microfluidic model of the BBB is designed using human cells and a brain-mimetic hydrogel. The in vitro BBB model replicates several key functions of the human BBB. This system has low permeability to small molecules and responds to inflammatory cues. The addition of GB cells to the model reveals that BBB function changes in a tumor-cell-population-dependent manner. Some GB cell populations lead to increased diffusive permeability while others induce increased immune cell binding. Together, these results indicate that this model can be used to investigate disease progression and drug delivery in GB.