Integrated platform for functional monitoring of 3D engineered brain-tissue for fundamental research and drug screening – 3DNeuroChip
Integrated platform for functional monitoring of 3D engineered brain-tissue for fundamental research and drug screening.
More than 10% of the world population (WHO 2016) suffers from a neuronal disorder. Thus, identifying therapeutic solutions to these diseases has become the prime target of governments and pharmaceutical industry. Unfortunately seldom functional data are available in human to help us in this task. Most functional studies have been carried out with mixed success in animal models. However their limited ability to replicate human diseases, their cost and ethical issues call for alternate solutions.
Development of a human in vitro model system capable of replicating key features of tissues to advances our understanding of human pathologies
The goal of this project is to integrate the expertise of the three partners to implement non-invasive technologies to monitor and model neuronal activity at a microscopic level in human-derived micro-tissues.
Tissue engineering methods have been optimized to standardize the production of 3D neuronal networks to 3D In vitro culture that enable high content data acquisition.
Transcriptomic changes were monitored by qPCR. Changes in protein expression was evaluated by westernblot and neuronal activity was monitored by multi electrodes array recording.
In vitro model that recapitulates an autistic phenotype was obtained by chemical induction.
Implantable electrodes were optimized to increase our sensing abilities.
Micro-devices were designed to provide spatial read-out necessary to characterize in vitro brain-tissue development and enable in silico modeling.
Machine learning was then carried out to formulate a model of in vitro neuronal networks.
- electrical activity recording
The signal to noise and the lifetime of the recording electrodes were increased by electrochemical treatments and validated over a 35 weeks period.
Micro-devices were fabricated to support implantable electrodes in in vitro 3D neuronal network to provide spatial 3D activity read-out necessary to characterize in vitro brain-tissue development.
The system was validated and a new generation of electrodes (hollow ring) was developed and tested.
- Biology
A protocol was developed to obtain by chemical induction an austistic phenotype. This phenotype was fully characterized as function of time by monitoring the neuronal activity over 5 weeks, and characterizing changes in transcriptomics via qPCR, and changes in protein expression by western blot.
- computational approaches deliver an analysis pipeline to interpret experimental data.
- the first in vitro autistic model that can provide more information that in vivo models
- a new generation of implantable electrodes with improved signal to noise
- the capability to characterize neuronal activity in three dimensions.
- a blue print of the computational pipe need to model in vitro data
We are now set to take this experiments to next level with humain cells obtained from cellular reprograming.
Our aim is to increase the number of 3D recording point available.
demande brevet EU : EP 22 306 404.9
submitted publications
Integrated platform for functional monitoring of 3D engineered brain-tissue for fundamental research and drug screening.
Neural disorders are affecting more than 10% of the world population (WHO 2016). Identifying therapeutic solutions to these diseases has become the prime societal interest. However, seldom functional data are available in human to help us in this task due to the technicity required to acquire these data. Additionally, most functional studies have been carried out with mixed success in animal models. Moreover, they have several limitations: the ethical issues associated with animal experiment, their high cost, and the growing realization of their limited ability to replicate the progression of human diseases.
Based on these facts, we now need in vitro model systems capable of replicating key features of tissues to advances our understanding of human pathologies. Such systems would be instrumental to set related studies up to an unprecedented dimension and could lead to better and faster development of pharmaceutical strategies to fight against neural disorders. With this aim in mind, the goal of this project is to integrate the expertise of the three partners to implement non-invasive in vitro and in silico technologies to monitor and model neuronal activity at a microscopic level in human-derived micro-tissues.
Project coordination
Sophie Pautot (SYNAXYS)
The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.
Partner
LAAS-CNRS Laboratoire d'analyse et d'architecture des systèmes du CNRS
IRIT REVA-IRIT
SYNAXYS
Help of the ANR 364,676 euros
Beginning and duration of the scientific project:
October 2019
- 42 Months