Newron3D

MIVT-7: Development of a 3D in vitro phenotypic platform for interrogating human iPSC-derived neuronal circuits

01.01.2018 bis 31.12.2020

Neurodegenerative disorders represent a dramatically growing condition in our aging society, but advances in finding a cure have been to date extremely limited, despite the significant efforts deployed by public and private stakeholders.
In the quest for developing new therapies, researchers are still largely dependent on 2 D in vivo experiments and animal models. These approaches poorly represent the multifaceted nature of neurodegenerative processes in the human bain and consequently have shown low predictive value in clinical studies.
To fill this gap, Newron3D will deliver a revolutionary human brain-on-a-chip (hBOC) phenotypic platform based on the integration of microfabrication technologies, electrode arrays and microfluidics to reconstruct, interrogate and image 3D brain circuits in a high-throughput format.
Human brain cell populations (neurons and glia) derived from induced pluripotent stem cells (iPSCs), grown within hydrogel scaffolds, will be employed to recreate 3D, brain-like multicellular architectures inside microfabricated bioreactors. Arrays of integrated microelectrodes will be used to non-invasively monitor the electrical activity of enclosed neuronal polulations across interconnecting circuits. Simultaneously, confocal microscopy will provide 3D structural information with sub-cellular resolution by fully robotic high content analysis (HCA). Due to the compact size of the microfluidic bioreactor, running each assay will only require a few thousand cells and few microliters of test compounds.
In combination with the use of iPSCs derived from neurodegenerative patients and healthy subjects, Newron3D will provide scientists and industry with a novel, high-throughput, brain-relevant in vitro system for exploring human disease mechanisms and evaluating efficacy and safety of newly developed compounds.