Pediatric Glioblastoma.
The Challenge.
Pediatric high-grade gliomas (pHGG) represent childhood and adolescent brain cancers that carry a rapid dismal prognosis. Since there is a need to overcome the resistance to current treatments and find a new way of cure, modeling the disease as close as possible in an in vitro setting to test new drugs and therapeutic procedures is highly demanding. Studying their fundamental pathobiological processes, including glutamatergic neuron hyperexcitability, will be a real advance in understanding interactions between the environmental brain and pHGG cells.
The Solution.
Organs-on-chip enable to recreate neurons/pHGG cell interactions with the development of a functional in vitro model co-culturing human-induced Pluripotent Stem (hiPS)-derived cortical glutamatergic neurons and pHGG cells and recording their electrophysiological modifications.
• DuaLink NeuroFluidics Devices & CNS NeuroFluidics Cultures
• hiPSC-derived glutamatergic neurons in Channel 1
• BT35, patient-derived cell line, or, UW479, commercialized pHGG line, in Channel 1
• Analyze of the electrical impact of pHGG cells on human glutamatergic neurons
Using organs-on-chip to study the functional impact of phGG cells on human glutamatergic neurons.
This Use Case shows the development of a functional in vitro co-culture model of human induced pluripotent stem cell (hiPS)-derived cortical glutamatergic neurons and pHGG-derived cell lines in compartmentalized microfluidic devices, and a process for recording electrophysiological changes in glutamatergic neurons.
• Differentiation and characterization of hiPSC-derived glutamatergic neurons (Nestin, Sox2, mGlurR2 & vGLUT1)
• Analysis of the electrical impact of pHGG cells on glutamatergic neurons
• Significant increase in the excitability of glutamatergic neurons in the presence of tumor cells
Test your compound on our ready-to-use NeuroFluidics Cultures with reference compound already on the market or having failed in the clinical phase.
Benefits.
Relevant in vitro model
The study shows the development of a functional in vitro model co-culturing human neurons and tumor cells into compartmentalized microfluidic devices and a process to record their electrophysiological modifications.
• Screening of potential drugs for their effectiveness in treating Pediatric Glioblastoma
High-throughput & interoperable solutions
NeoBento™, the standard format for NeuroFluidics Devices chips, available up to 4 QuarterBentos™ (up to 16 chips).
• Standard ANSI format (96-well plate)
• Pump-free & expensive equipment-free
• Standard equipment (liquid handling & imaging) compatibility
Compartmentalization & MEA-recording
Recreate the brain microenvironment to co-culture neurons and tumor cells.
• Co-culture and connection of neurons & immune cells
• Control of media exchange and cell seeding density
• Analysis of the electrical impact of tumor cells on neurons
Readouts compatibility
In-depth reading of the data to better understand the study results and potential implications.
• Electrophysiological recording (MEA)
• Imaging (Immunofluorescence, Calcium Imaging…)
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• Biochimic analysis (ELISA, Lysis cells analysis, Liquid Chromatography…)
Our Offers.
NETRI Services.
• Technological Transfert
• FTE & Screening Services
• Co-development
• Analytical Services
NETRI Products.
• NeuroFluidics Devices
• NeuroFluidics Cultures
• NeuroFluidics Digital
• Training & Organs-on-chip Kits
Summary.
• [MicroTas] Co-culture model of glutamatergic neurons and pediatric high-grade glioma cell lines in microfluidic devices to evaluate electrophysiological impact
• [2023] Chemotherapy-Induced Peripheral Neuropathy-On-Chip Model : Utilizing the strength of compartmentalization
• [2022] The DuaLink Chips how to improve reproducibility in compartmentalized co-cultures
• Fuchs, Q., Batut, A., Gleyzes, M., Rontard, J., Miny, L., Libralato, M., Vieira, J., Debis, D., Larramendy, F., Honegger, T., Messe, M., Pierrevelcin, M., Lhermitte, B., Dontenwill, M., Entz-Werlé, N. (2021). Co-culture of Glutamatergic Neurons and Pediatric High-Grade Glioma Cells Into Microfluidic Devices to Assess Electrical Interactions. J. Vis. Exp. (177), e62748, https://doi.org/10.3791/62748
• Rontard J, Maisonneuve BGC, Honegger T. (2023). Expanding human-based predictive models capabilities using organs-on-chip: A standardized framework to transfer and co-culture human iPSCs into microfluidic devices. Arch Pharm Pharma Sci. ; 7: 017-021. https://doi.org/10.29328/journal.apps.1001039
• Maisonneuve, B. G. C., Libralesso, L., Miny, L., Batut, A., Rontard, J., Gleyzes, M., … & Honegger, T. (2022). Deposition chamber technology as building blocks for a standardized brain-on-chip framework. Microsystems & Nanoengineering, 8(1), 86. https://doi.org/10.1038/s41378-022-00406-x
• Maisonneuve, B. G. C., Vieira, J., Larramendy, F., & Honegger, T. (2021). Microchannel patterning strategies for in vitro structural connectivity modulation of neural networks. BioRxiv, 2021-03. https://doi.org/10.1101/2021.03.05.434080
• DuaLink Protocol
• Sensory Neurons Protocol
• Fixation & Immunostaining Protocol
• DuaLink MEA
• Tumor cells
• Live Dead Assays
• Electrophysiology
