Nerve Injury.
The Challenge.
Peripheral nerves are made of motor and sensory nerves, two very distinct types of neurons that are linked but each have their specific function. Accidents, surgeries and compressions (tumor, carpial canal syndrome) are examples of situations where traumatic injury to the spinal cord or nerves can induce neuropathic pain in addition to the debilitating motor and sensory symptoms. Two main axes of treatments have an important impact on patients’ quality of life: (i) regenerative medicine to reconstruct and regenerate nerve (ii) efficient pain relief. Conventional in vitro models are unable to isolate somas and neurites from neurons, thus limiting the discovery of regenerative therapies.
The Solution.
Organs-on-Chip enable the reproduction of highly segregated neural circuits, isolating neuron somas from their axons to mimic human neuroanatomical architecture for more relevant injury or treatment paradigms. This translational nerve injury platform enables the discovery of regenerative therapies. The microchannel technology used enhances axonal projections, providing an improved environment for neurotrophic or neurodegenerative readouts. The microfluidic isolation and architecture of our devices offer the advantage of targeting only neurites and not cell bodies as in conventional in vitro models.
• DuaLink Shift NeuroFluidics Devices & PNS NeuroFluidics Cultures
• hiPSC-derived sensory neurons somas in channel 1 & projections in channel 3
• Nocadazole or Staurosporine in channel 2
• Localized neurite injury with a reproducible protocol & neurite regeneration post-injury
Using organs-on-chip to model motor neurons injury.
Mirroring current in vivo models, such as nerve crush injury or nerve ligation which aim to mimic human nerve trauma, we have created a reproducible and standardized injury, cutting, motor and sensory axons only using a short and targeted detergent application. This platform enabled us to compare axonal regeneration after treatment with a neurotrophic molecule or a drug inhibiting neurite growth.
• Microtubule destabilization by nocodazole as an internal neurodegenerative control
• Enhancing neurite outgrowth by staurosporine, a broad-spectrum protein kinase inhibitor, used as an internal neurotrophic control
Screen your compound in our already industrial digital library with different combinatory responses and/or doses for IND/MAA submission.
Using organs-on-chip to model sensory neurons injury.
Mirroring current in vivo models, such as nerve crush injury or nerve ligation which aim to mimic human nerve trauma, we have created a reproducible and standardized injury, cutting, motor and sensory axons only using a short and targeted detergent application. This platform enabled us to compare axonal regeneration after treatment with a neurotrophic molecule or a drug inhibiting neurite growth..
• Nocodazole more potent on axoCells™ sensory neurons vs. iCell motor neurons
• Staurosporine less effective on iCell motor neurons, at the same concentration
• Detection of differences in efficacy depending on the cell model used
Screen your compound in our already industrial digital library with different combinatory responses and/or doses for IND/MAA submission.
Benefits.
Relevant in vitro model
Humanized in vitro traumatic injury models to recreate human anatomical architecture.
• Human motor and sensory neurons models
• Discovery of regenerative therapeutics
• Enhance axonal projections
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 & Fluidic isolation
Compartmentalized microfluidics devices enabling injury or treatment paradigms aligned with real life situations.
• Target only neurites and not cell bodies
• Improve environment for neurotrophic readouts
• Mimic human nerve trauma
Readouts compatibility
In-depth reading of the data to better understand the study results and potential implications.
• Electrophysiological recording (MEA)
• Imaging (Immunofluorescence, Calcium Imaging…)
.
• 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.
• [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
• 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
• Embryonic DRG Neurons
• Live Dead Assays
