Biology subjects

Peyrin, J.-M.

Publications and source records attributed to Peyrin, J.-M..

4 recordsLinked to original sources

bioRxiv2026

Scaffold-Free Acoustic Levitation Platforms Enable Scalable Culture of Neuronal Spheroids and Assembly of Layered Cortico - Striatal Assembloids

Engineering three-dimensional neuronal tissues with defined architecture and functional connectivity remains a critical challenge for applications in disease modeling, drug discovery, and regenerative medicine. Recently, a variety of fabrication methods have arisen, such as bioprinting or manual assembly of organoids, but often struggle with scalability, reproducibility, or maintaining cell viability. Here, two scaffold-free acoustic levitation bioreactors are introduced: one optimized for the culture of uniform neuronal spheroids, and another designed for the structuration of assembloids composed of distinct neuronal identities. Using acoustic standing waves, these platforms enable the contactless manipulation of cells and aggregates, facilitating the formation of highly viable functionally mature spheroids. This study shows that both striatal and cortical cell aggregates formed in acoustic levitation self-organize into spheroids within 24 hours and remain viable up to 10 days under these particular culture conditions without medium renewal. These neuro-spheroids demonstrate healthy development with increased growth and typical terminal differentiation and synaptic maturation. Moreover, concentric cortico-striatal assembloids were successfully structured and cultivated using optimized acoustofluidic chips. Offering versatile and scalable tools for engineering complex neuronal networks, acoustic levitation reveals itself as an innovative approach to 3D neuronal tissue modeling, with broad implications for bioengineering, regenerative medicine and fundamental neuroscience research.

bioengineering↗

bioRxiv2024

Microgravity stimulates network activity of 3D neuronal spheroids in an acoustic trap

Among biological models, cell culture constitutes an important paradigm that allows rapid examination of cell phenotype and behavior. While cell cultures are classically grown on a 2D substrate, the recent development of organoid technologies represents a paradigmatic shift in biological experimentation as they pave the way for the reconstruction of minimalist organs in 3D. Manipulating these 3D cell assemblies represents a considerable challenge. While there is growing interest in studying the behavior of cells and organs in the space environment, manipulating 3D cultures in microgravity remains a challenge. But with cellular research underway aboard the International Space Station (ISS), optimizing techniques for handling 3D cellular assemblies is essential. Here, in order to cultivate 3D models of spheroids in microgravity, we developed and used an acoustic bioreactor to trap levitating cellular organoids in a liquid cell culture medium. Indeed, in a Bulk Acoustic Wave (BAW) resonator, spherical objects, such as cells, can be maintained in an equilibrium position, inside a resonant cavity, away from the walls. In the acoustic levitation plane, gravity is counterbalanced by the acoustic radiation force (ARF) making it possible to maintain an object even in weightlessness. A dedicated setup was designed and built to perform live calcium imaging during parabolic flights. During a parabolic flight campaign, we were able to monitor the calcium activity of 3D neural networks trapped in an acoustic field during changes in gravity during different parabolas. Our results clearly indicate a change in calcium activity associated with variations in gravity.

biophysics↗

bioRxiv2022

Human glioblastoma cell motility depends on the activity of the cysteine metabolism enzyme 3-Mercaptopyruvate sulfurtransferase

Cancer cells in similar functional states are found in all glioblastoma, despite the genomic heterogeneity observed between and within these brain tumors. Metabolism being downstream of all signaling pathways regulating cell behaviors, we looked for metabolic weaknesses in link with motility, a key functional state for glioblastoma aggressiveness. A signature-driven data reduction approach highlighted motile cells present in thirty tumors from four independent single-cell transcriptomic datasets. Analyses integrating trajectory modeling disclosed, as characteristic of motile cells, enhanced oxidative stress coupled with mobilization of the cysteine metabolism enzyme 3-Mercaptopyruvate sulfurtransferase (MPST). The soundness of this prediction was verified using migration and invasion assays with patient-derived cells and tissue organoids. Pharmacological and genetic manipulations showed that enhanced ROS production and MPST activity are required for the cells motility. Biochemical assays indicated that MPST acts by protecting protein cysteine residues from dismal hyperoxidation. In vivo, MPST knockdown translated in reduced tumor burden, and a robust increase in mice survival. These results show that enhanced oxidative stress coupled with MPST mobilization plays a key role in glioblastoma cell motility.

cancer biology↗

bioRxiv2021

Quantitative study of alpha-synuclein prion-like spreading in fully oriented reconstructed neural networks reveals non-synaptic dissemination of seeding aggregates

The trans-neuronal spread of protein aggregates in a prion-like manner underlies the progression of neuronal lesions in the brain of patients with synucleinopathies such as Parkinsons disease. Despite being studied actively, the mechanisms of alpha-synuclein (aSyn) aggregates propagation remain poorly understood. This hinders the development of therapeutic approaches aiming at preventing the spatial progression of intracellular inclusions in neural networks. To assess the role of synaptic structures and neuron characteristics in the transfer efficiency of aggregates with seeding propensity, we developed a novel microfluidic culture system which allows for the first time to reconstruct in vitro fully oriented and synaptically connected neural networks. This is achieved by filtering axonal growth with unidirectional "axon valves" microchannels. We exposed the presynaptic compartment of reconstructed networks to well characterized human aSyn aggregates differing in size: Fibrils and Oligomers. Both aggregates were transferred to postsynaptic neurons through active axonal transport, albeit with poor efficiency. By manipulating network maturity, we compared the transfer rate of aggregates in networks with distinct levels of synaptic connectivity. Surprisingly, we found that transfer efficiency was lower in mature networks with higher synaptic connectivity. We then investigated the seeding efficiency of endogenous aSyn in the postsynaptic population. We found that exposure to Fibrils, and not Oligomers, resulted in low efficiency trans-neuronal seeding which was restricted to postsynaptic axons. Finally, we assessed the impact of neuron characteristics and aSyn expression on the propagation of aSyn aggregates. By reconstructing chimeric networks, we found that neuron characteristics, such as the brain region from which they originate or aSyn expression levels, did not significantly impact aggregates transfer, and observed no trans-neuronal seeding where the presynaptic population did not express aSyn. Overall, we demonstrate that this novel platform uniquely allows the quantitative interrogation of original aspects of the trans-neuronal propagation of seeding pathogenic entities.

neuroscience↗