WETWARE.
NEURONAL CULTURES.
2D Cultures.
2D neuronal cultures are derived from human induced pluripotent stem cells (hiPSC) and include the main functional subtypes. These co-cultures are designed to recreate physiologically relevant neuronal circuits in NETRI's compartmentalized microfluidic devices.
• Glutamatergic Neurons.
• GABAergic Neurons.
• Motor Neurons.
• Sensory Neurons.
• Dorsal Horn Neurons.
• Astrocytes.
Cultures are validated by maturation markers (MAP2, ChAT, VAChT...) and show robust electrophysiological activity.
3D Cultures.
Cerebral organoids reproduce the early stages of human brain development, with realistic tissue architecture and complex cellular organization.
In collaboration with CEA and Supbiotech, NETRI has optimized the culture of human brain organoids in its MultiFluidics devices, improving homogeneous growth and reproducibility. This provides a reliable starting point for toxicity testing. Using H2O2 as a proof of concept, we've developed decision tree algorithms to perform noninvasive quality control during culture and explore the impact of toxins.
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NEURONS & MUSCLE CULTURES.
NeuroMuscular Junction.
NETRI has developed a neuromuscular junction (NMJ) model by co-culturing hiPSC motor neurons and hiPSC myotubes or primary human muscle cells, integrated in our NeuroFluidics MEA devices. This physiologically relevant model enables us to observe a functional cholinergic synapse, validated by the expression of α-bungarotoxin on postsynaptic receptors, and by synchronous electrophysiological activity. The NMJ model is stable for over 20 days.
The optional addition of sensory neurons and astrocytes can also enable more complex circuits to be modeled, including the reflex loop.
SKIN CULTURES.
Innervated Skin.
NETRI has developed a proof-of-concept 2D model of innervated skin combining primary human keratinocytes and sensory neurons derived from hiPSC stem cells. With MEA compartmentalized microfluidic devices, this model makes it possible to measure the electrophysiological activity of neurons and observe their dynamic interaction with skin cells. This represents a functional sensory model for exploring the cutaneous response to stimulation.
The platform makes it possible to evaluate the effect of compounds on sensory nerve endings under acute or chronic conditions, generating electrophysiological signatures that can be directly exploited for molecule screening or validation.
Pre-Vascularized Skin.
The MultiFluidics platform (Duplex™) device integrates a 2D model of pre-vascularized skin co-cultured with keratinocytes and primary human endothelial cells. Thanks to a transparent nanoporous membrane, exchanges between compartments are controlled, enabling the progressive development of an underlying vasculature for studying vascular transport, permeability and regeneration.
This model offers a relevant environment for testing the transdermal diffusion of compounds
ORGANOIDS & SPHEROIDS.
Liver Organoids.
Liver organoids grown in BioMIMESYS® Liver faithfully reproduce the key functions of the human liver :
• +20 to 30x albumin secretion compared with 2D cultures.
• High expression of CYP450 enzymes (CYP3A4, CYP1A1/2, CYP2B6).
• Formation of a network of canaliculi (Actin/MRP2).
• Response to treatment (e.g. lipid accumulation with amiodarone).
Liver organoids have already been used for applications in toxicology screening, metabolism and liver diseases (NASH, steatosis, fibrosis).
Adipose Tissue Organoids.
Human pre-adipocytes grown in BioMIMESYS® differentiate efficiently and retain their functionality for up to 2 months:
• Adapted ECM architecture (HA + collagens I and VI).
• Physiological elasticity (0.45 kPa).
• Compatible with primary cells and iPSCs.
Adipose Tissue organoids have already been used for applications in lipid metabolism, obesity, diabetes, nutritional screening.
Pancreas Spheroids.
PANC-1 cells grown in BioMIMESYS® form growing, homogeneous spheroids in BioMIMESYS®, providing a stable platform for:
• Analysis of tumor growth.
• Assessing the cytotoxicity of chemotherapies.
• The study of invasion and responses in the tumor microenvironment.
Pancreas spheroids have already been used for applications in pancreatic oncology, 3D tumor modeling, therapeutic response.
Organoids For Oncology.
BioMIMESYS® customizes the tumor microenvironment to better predict treatment efficacy. It is possible to modulate the rigidity (e.g. 1 kPa) and composition of the ECM matrix to simulate different tumor stages or types:
• Measured impact on cell proliferation.
• Marker monitoring (e.g. CD44, MDA-MB-231 spheroids, MCF7).
• Possibility of co-culturing with human immune cells.
BioMIMESYS® Oncology have already been used for applications in immuno-oncology, development of targeted therapies, resistance studies.
EXTRACELLULAR MATRIX.
The Challenge.
Conventional approaches - hydrogels, solid scaffolds or suspension cultures - struggle to recreate an extracellular matrix (ECM) faithful to that of native tissues. As a result, cultured cells lack the mechanical and biochemical signals they need to function properly, and the in vitro data they produce are difficult to transpose in vivo.
BioMIMESYS hydroscaffold addresses this critical situation for the development of physiologically relevant models, particularly for complex organs such as the brain, liver or tumor tissue by reproducing ECM with all physicochemical & biological properties.
ECM By Organs.
Developed by HCS Pharma, BioMIMESYS® technology is now integrated into NETRI's organs-on-chip devices. BioiMIMESYS is a hydroscaffold™: an innovative blend between a solid scaffold and a hydrogel, based on hyaluronic acid and collagen. It makes it possible to recreate, in standard format (24 or 96 wells), an ECM specific to each organ - healthy or pathological - while retaining the essential biological, chemical and mechanical properties. This multi-organ compatibility makes BioMIMESYS® a central component of our Wetware platforms:
• BioMIMESYS Liver.
• BioMIMESYS Adipose Tissue.
• BioMIMESYS Brain.
• BioMIMESYS Oncology.
MAIN PIPELINE.
Oncology.
Explore pain management and toxicity for oncology drug development with the Neurons as a Sensor (NaaS) suite.
• Chemotherapy-Induced Peripheral Neuropathy.
• Emetic Response.
• Other Possibilities.
Vaccinology.
Explore pain and inflammation of injection site for vaccine development with the Neurons as a Sensor (NaaS) suite.
• Injection Pain.
• Muscular Response (NMJ).
• Other Possibilities.
Dermatology.
Test the effects of your products on our innervated skin or sensory neurons alone models.
• Atopic Dermatitis, Psoriasis, Skin irritation, Pruritus, Sensitization.
• Diabetes, Botox-like, Burn victim.
SECONDARY PIPELINE.
Neurodegenerative Diseases.
Model and/or diagnose neurodegenerative diseases with our brain-on-chip.
• Alzheimer's, Parkinson's, ALS, Dementia.
• Modeling.
• Diagnosis.
Neurotoxicology.
Explore toxicology with the Neurons as a Sensor (NaaS) suite.
• Food & Chemical Safety.
• Pesticide screening.
• Pharma neurotoxicology.
