Seminar "In vitro biomimetic microfluidic device to resemble pseudopalisade formation and glioblasto
Sala de Juntas, Edificio Politécnico Campus de Ciudad Real, 12:00
Glioblastoma is one of the most invasive tumours. During tumour development hypercellularized regions, named pseudopalisades, are observed. These pseudopalisades seem to play a critical role on GBM spreading and invasion, however the pseudopalisade formation mechanism remains challenging. One of the hypothesis is that pseudopalisades are waves of migrating glioblastoma cells guided by oxygen and nutrient depletion caused by the uncontrolled proliferation and blood vessel occlusion. In our group we have developed a new microfluidic device that mimics this pseudopalisade generation and invasion. U-251 cells, a glioblastoma cell line, are embedded within a collagen hydrogel in a microfluidic device. Controlling medium flow through the lateral microchannels we can mimic the thrombotic event associated to this disease. Cell metabolism creates a nutrient starvation, triggering a strong migratory process which finally leads to the pseudopalisade generation. Using confocal microscopy we observed that pseudopalisade formation occurs in different sequential steps: an initial stage showing only moderate migration. In a second stage, an extremely intense mesenchymal migration is evidenced, leading to the pseudopalisade formation. Finally, this completely formed pseudopalisade starts to invade collectively the hydrogel towards the nutrient source.