Biology subjects

Honegger, T.

Publications and source records attributed to Honegger, T..

6 recordsLinked to original sources

bioRxiv2025

The NaaS Methodology applied to modeling chemotherapy-induced peripheral neuropathy with human hiPSC neurons

The Neuron-as-a-Sensor (NaaS) methodology is a human-relevant platform designed to detect compound-induced effects by capturing functional changes in neuronal activity. This is achieved by integrating hiPSC-derived neuronal cultures, compartmentalized MEA microfluidic devices, a detailed electrophysiology paradigm and a standardized analysis pipeline. Applied to chemotherapy-induced peripheral neuropathy (CIPN), NaaS leverages electrophysiological profiling to capture alterations in neuronal excitability beyond cytotoxicity. Using paclitaxel and oxaliplatin as reference compounds, we demonstrated drug-specific, time-dependent changes in spontaneous and thermally evoked activity that align with their distinct clinical neuropathic phenotypes. Dimensionality reduction of electrophysiological metrics enabled construction of a functional discrimination map, allowing robust separation of compound signatures from vehicle controls. These findings highlight the ability of NaaS to model clinically relevant neurotoxic effects in a scalable manner, supporting its application in both adverse effect prediction and therapeutic screening.

bioengineering↗

bioRxiv2025

A robust and comprehensive quality control of cerebral cortical organoids: methodology and validation

Cerebral organoids hold great promise for neuroscience research as complex in vitro models that mimic human brain development. However, they face significant challenges related to quality and reproducibility, leading to unreliability in both academic and industrial contexts. Discrepancies in morphology, size, cellular composition, and cytoarchitectural organization limit their application in biomedical studies, particularly in disease modeling, drug screening, and neurotoxicity testing, where consistent models are essential. Critically, current methods for organoid characterization often lack standardization and rely heavily on subjective assessments, restricting their broader applicability. In this study, we developed a comprehensive Quality Control (QC) framework for 60-days cortical organoids. Five key criteria: morphology, size and growth profile, cellular composition, cytoarchitectural organization, and cytotoxicity, are evaluated using a standardized scoring system. We implemented a hierarchical approach, beginning with non-invasive assessments to exclude low-quality organoids (Initial Scoring), while reserving in-depth analyses for those that passed the initial evaluation (Final Scoring). To validate this framework, we exposed 60-day cortical organoids to graded doses of hydrogen peroxide (H2O2), inducing a spectrum of quality outcomes. The QC system demonstrated its robustness and reproducibility by accurately discriminating organoid quality based on objective and quantifiable metrics. This standardized and user-friendly framework for quality assessment not only minimizes observer bias but also enhances the reliability and comparability of cerebral organoid studies. Additionally, its scalability makes it suitable for industrial applications and adaptable to other organoid types, offering a valuable tool for advancing both fundamental and preclinical research.

neuroscience↗

bioRxiv2024

Neurons as biosensors for discriminating neurological disorders in a brain-on-chip platform: Application to Alzheimer s Disease using patient CSF

Alzheimers disease (AD) is characterized by the accumulation of aggregated amyloid beta peptide (A{beta}) leading to progressive neuronal loss and dysfunction. Current ADs diagnosis involves biomarkers assays in cerebrospinal fluid (CSF) as A{beta} to validate the diagnosis. However, these methods are time-consuming, expensive, and can result in inaccurate diagnoses by not accounting for differential diagnose. To overcome these challenges, researchers are exploring new technologies for detecting AD biomarkers in biological fluids, though progress is hindered by an incomplete understanding of AD mechanisms and CSF composition. In this study, we used a standardized microfluidic platform to investigate the effects of synthetic A{beta} peptides and cerebrospinal fluid (CSF) from AD and healthy patients on neuronal functional activity. First, human neurons derived from induced pluripotent stem cells (iPSCs) were characterized. Then, to modulate the functional activity of neurons, tetrodotoxin (TTX), a specific sodium channel blocker, was used as a control for inhibiting neuronal activity. Subsequently, glutamatergic neurons were chronically exposed to A{beta}O and patients CSF. MEA recordings were performed before and after the treatments to assess changes in network activity. Our results demonstrated that extracting key electrophysiological metrics allows for discrimination between healthy and AD CSF samples. This system could offer the potential for differential diagnosis and development of personalized therapeutic strategies.

neuroscience↗

bioRxiv2021

Deposition chamber technology as building blocks for a standardized brain-on-chip framework

In vitro modeling of human brain connectomes is key to explore the structure-function relationship of the central nervous system. The comprehension of this intricate relationship will serve to better study the pathological mechanisms of neurodegeneration, and hence to perform improved drug screenings for complex neurological disorders, such as Alzheimers and Parkinsons diseases. However, currently used in vitro modeling technologies lack potential to mimic physiologically relevant neural structures, because they are unable to represent the concurrent interconnectivity between myriad subtypes of neurons across multiple brain regions. Here, we present an innovative microfluidic design that allows the controlled and uniform deposition of various specialized neuronal populations within unique plating chambers of variable size and shape. By applying our design, we offer novel neuro-engineered microfluidic platforms, so called neurofluidic devices, which can be strategically used as organ-on-a-chip platforms for neuroscience research. Through the fine tuning of the hydrodynamic resistance and the cell deposition rate, the number of neurons seeded in each plating chamber can be tailored from a thousand up to a million, creating multi-nodal circuits that represent connectomes existing within the intact brain. These advances provide essential enhancements to in vitro platforms in the quest accurately model the brain for the investigation of human neurodegenerative diseases.

bioengineering↗

bioRxiv2021

Neurite growth kinetics regulation through hydrostatic pressure in a novel triangle-shaped neurofluidic system

Microfluidic neuro-engineering design rules have been widely explored to create in vitro neural networks with the objective to replicate physiologically relevant structures of the brain. Several neurofluidic strategies have been reported to study the connectivity of neurons, either within a population or between two separated populations, through the control of the directionality of their neuronal projections. Yet, the in vitro regulation of the growth kinetics of those projections remains challenging. Here, we describe a new neurofluidic chip with a triangular design that allows the accurate monitoring of neurite growth kinetics in a neuronal culture. This device permits to measure the maximum achievable length of projecting neurites over time and to report variations in neurite length under several conditions. Our results show that, by applying positive or negative hydrostatic pressure to primary rat hippocampal neurons, neurite growth kinetics can be tuned. This work presents a pioneering approach for the precise characterization of neurite length dynamics within an in vitro minimalistic environment.

neuroscience↗

bioRxiv2021

Microchannel patterning strategies for in vitro structural connectivity modulation of neural networks

Compartmentalized microfluidic chips have demonstrated tremendous potential to create in vitro minimalistic environments for the reproduction of the neural circuitry of the brain. Although the protocol for seeding neural soma in these devices is well known and has been widely used in myriad studies, the accurate control of the number of neurites passing through the microchannels remains challenging. However, the regulation of axonal density among different groups of neurons is still a requirement to assess the inherent structural connectivity between neuronal populations. In this work, we report the effect of microchannel patterning strategies on the modulation of neuronal connectivity by applying dimensional modifications on microchannel-connected microfluidic chambers. Our results show that those strategies can modulate the direction and the number of neuronal projections of passage, therefore regulating the strength of the structural connections between two populations of neurons. With this approach, we provide innovative microfluidic design rules for the engineering of in vitro physiologically relevant neural networks.

neuroscience↗