Inflammatory Bowel Disease.
The Challenge.
Inflammatory bowel diseases (IBD) are complex chronic inflammatory disorders of the gastrointestinal (GI) tract. Recent evidence suggests that the gut-brain axis may be pivotal in gastrointestinal and neurological diseases, especially IBD. Modeling the gut-brain axis involved in IBD, which involves bilateral communication of neuronal, hormonal, metabolic, immunological and microbial signals, remains a challenge due to its high biological complexity, the involvement of different cell types and physical communication pathways, and the lack of study models. These include animal models, which do not allow for the study of the pathophysiological effects of IBD on mucosal nerve cells, and gut-on-chip models, which do not incorporate nerve cells and analysis of their electrical activity (MEA).
The Solution.
Modeling the gut-brain axis and studying neuron-immune cell communication. The DuaLink Shift comprises three compartments with an asymmetric channel, enabling soma and neurites to be isolated by microchannels to create synaptic transmission. The microfluidic device was coupled to MEA to record the electrophysiological signal as a function of conditions and analyze neurite functionality.
• DuaLink Shift MEA NeuroFluidics Devices & CNS NeuroFluidics Cultures
• hiPSC-derived glutamatergic neurons in Channel 1
• MoDC in either Channel 1, Channel 2 or Channel 3 depending on conditions
• Analyze of the electrical impact of MoDC cells on human glutamatergic neurons
Using organs-on-chip to study the functional impact of MoDC cells on human glutamatergic neurons.
The use case demonstrates (i) the association of human neuronal and immune cells in DuaLink Shift and (ii) access to a non-invasive analysis method to study the communication between these two cell types in the context of inflammation to model neuro-immune interaction in the inflammatory condition of IBD.
• Observation of IL-6 secretion induced by the addition of MoDCs
• Induction of changes in the electrical activity of glutamatergic neurons by the addition of MoDCs
• Creation of a specific model of neuron-immune cell communication with potential implications for understanding the impact of immunological signaling pathways on neuronal activity
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.
Bidirectional communication
The study explores gut-brain communication in IBDs, focusing on neuroimmune interactions using a microfluidic device.
• A new approach coupled with MEA to model the neuro-immune system
• Communication of neuronal, hormonal, metabolic, immunological and microbial signals
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
This device allows first the precise deposition of cells in a chamber directly on MEA.
• Co-culture and connection of neurons & immune cells
• Control of cell seeding density and homogeneity on MEA
• Control of media exchange, which is a critical step for human neural progenitor differentiation directly into devices
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.
• [FENS] An Organ on chip platform to evaluate neuro immune signal transmission using human cells
• [2022] The DuaLink Chips how to improve reproducibility in compartmentalized co-cultures
• Gabriel-Segard, T.; Rontard, J.; Miny, L.; Dubuisson, L.; Batut, A.; Debis, D.; Gleyzes, M.; François, F.; Larramendy, F.; Soriano, A.; et al. (2023). Proof-of-Concept Human Organ-on-Chip Study: First Step of Platform to Assess Neuro-Immunological Communication Involved in Inflammatory Bowel Diseases. Int. J. Mol. Sci., 24, 10568. https://doi.org/10.3390/ ijms241310568
• 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
• CNS
• NeuroFluidics Cultures Pipeline
• Human MoDCs
• Live Dead Assays
• Electrophysiology
