Biology subjects

Di Lisa, D.

Publications and source records attributed to Di Lisa, D..

2 recordsLinked to original sources

bioRxiv2026

Functional human neurospheroids recapitulate key features of cortical complexity

BackgroundThree-dimensional in vitro neuronal cultures have emerged as promising platforms for modelling human brain function and disease under controlled conditions. However, their ability to recapitulate in vivo-like complexity and rich dynamics remains underexplored. In this study, we developed and characterized neurospheroids derived from human induced pluripotent stem cells (hiPSCs) to investigate how key features -- three-dimensionality, cellular heterogeneity, and modular organization -- contribute to replicating brain-like network dynamics. MethodsWe engineered neurospheroids with varying excitatory/inhibitory ratios and assembled them into modular constructs (assembloids), evaluating their electrophysiological activity using high-density micro-electrode arrays. We assessed spontaneous and evoked activity through established metrics of dynamical richness and perturbational complexity. ResultsOur findings show that three-dimensionality and modularity significantly enhance the richness and complexity of network activity, approaching levels observed in vivo, while cellular heterogeneity contribute to functional aspects of the network, such as nuanced activity patterns, dynamical variability, and modular coordination. ConclusionsOur work highlights the critical role of spatial organization in reproducing brain-like activity and provide a foundation for future studies using patient-derived neurospheroids to model disease-specific dynamics.

bioengineering↗

bioRxiv2023

Human-derived cortical neurospheroids coupled to passive, high-density and 3D MEAs: a valid platform for functional tests

With the advent of human-induced pluripotent stem cells (hiPSCs) differentiation protocols, different methods to create in-vitro human-derived neuronal networks have been proposed. Although monolayer cultures represent a valid model, adding three-dimensionality would make them more representative of an in-vivo environment. Thus, human-derived neurospheroids and brain-organoids are becoming increasingly used for in-vitro disease modeling. Achieving control over the final cell composition and investigating the exhibited electrophysiological activity is still a challenge. Thence, platforms capable of measuring and characterizing the functional aspects of these samples are needed. Here, we propose a method to rapid generate neurospheroids of human origin with control over cell composition that can be used for functional investigations. We show a characterization of the electrophysiological activity exhibited by the neurospheroids by presenting for the first-time results from the main micro-electrodes arrays (MEAs) types available on the market (passive electrode, C-MOS electrodes, 3D electrodes). Neurospheroids grown in free culture and transferred on MEA exhibited functional activity that can be chemically and electrically modulated. Our results indicates that this model holds great potential for in-depth study of signal transmission to drug screening, disease modeling and offers a reproducible and stable platform for in-vitro functional testing.

bioengineering↗