Glioma on a chip: Probing Glioma Cell Invasion and Gliomagenesis on a Multiplexed Chip

Projektbeschreibung

3D-In-vitro-Modell des Glioms

Gliome sind die häufigsten primären Hirntumore und haben ihren Ursprung im Stützgewebe des Gehirns. Mangels geeigneter Krankheitsmodelle gestalten sich Tests neuer Wirkstoffkandidaten aber bislang schwierig. Das EU-finanzierte Projekt GliomaChip entwickelt mittels eines biotechnologischen Bottom-up-Ansatzes und Mikrofluidik 3D-Modelle der Mikrostruktur von Zellkonstrukten, um daran verschiedenste Aspekte der Gliombiologie wie Migration und Angiogenese zu untersuchen. Langfristig soll ein 3D-In-vitro-Modell eines Gliom-on-a Chip entwickelt und die komplexe In-vivo-Mikroumgebung des Glioms simuliert werden, um neue Wirkstoffe zu testen und das Patientenmanagement insgesamt zu verbessern.

Ziel

28% of all primary brain tumors and central nervous system tumors and 80% of malignant tumors are gliomas, which arise from the supportive tissues in the brain. Yet, our ability to effectively treat these cancers is limited by our knowledge of the disease and our ability to test new treatments on accurate models. Advances in microfluidics and cell encapsulation within hydrogels have made significant strides in trying to meet these needs, but the potential to use these technologies for engineering physiologically relevant tissue models has yet to be fully realized. Here, we propose to investigate cancer biology using a microfluidic device with three-dimensional (3D) micro-patterned cellular constructs that may be subjected to flow through microfluidic channels. Using the developed model, we aim to understand the cellular gliomagenesis, glioma cell migration, and angiogenesis and further test drug susceptibility to demonstrate the relevance of the proposed model. To achieve these goals, I have formulated an innovative and interdisciplinary strategy based on my research experience in bottom-up tissue engineering and microfluidics, and brought together a strong team. First, I will receive an intensive training at the Max Planck Institute for Intelligent Systems on micro-robotics to strengthen the bridge between the fields of micro-robotics and bottom-up tissue engineering. Then, I will get a training at the Harvard Medical School on glioma cell culture and cell extraction from a mouse model. Finally, all these efforts will be integrated into the development of an in vitro 3D glioma-on-a-chip model mimicking the complex in vivo microenvironment of glioma. The successful completion of this timely and innovative project will result in an advanced microphysiological system that will contribute to the competitiveness of Europe in the fields of cancer management, pharmaceutics, and personalized medicine.