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Microfluidic chambers for establishing physiological and pathological human iPSC-derived neuronal circuits

Project description

Functional brain tissue kits provide a standardised test bench for studying brain circuitry

The human brain has billions of neurons and even more non-neuronal cells that are actually highly organised. The specific interconnections are prerequisite to the myriad functions that make us human – and quite challenging to recreate in cell culture. BrainCircuit-on-chip is changing the rules of the game with a simplified system that achieves patterned and functional connections among several neuronal cell types. Further, the system is easily subjected to pharmacological or other perturbations and dynamic changes can be observed in high-resolution, real-time. In short, it is a major breakthrough for studies of neuronal circuitry and the team is planning to make it available in a frozen toolkit along with instructions to support basic and applied research.

Objective

In vitro cultures of brain cells generate an ease and accessible ensemble of neurons In vitro cultures of brain cells generate an ease and accessible ensemble of neurons which has been invaluable for innumerable cellular and molecular studies. However, brain tissue dissociation and neuronal plating in vitro causes a complete loss of the original connections present into the brain tissue. Therefore, in vitro neuronal cultures do not allow to model specific neuronal circuits and study their specific properties. The same limitation is valid for human stem cell-derived neuronal cell cultures. In fact, several neuronal cell types can be differentiated from human iPS cells (iPSCs), but without any organization in terms of connectivity or synaptic specificity. We have established a microfluidic platform, named BrainCircuit-on-chip, which allows to growth human iPSC-derived neurons with a stereotyped organization and to establish patterned connections between different neuronal cell types. These microchips contain a central chamber where synapses between the two neuronal cell types are generated establishing the correct functional integration between the two neuronal populations. PDMS-microfluidic chambers are transparent and enables high-power and time-lapse imaging in the different neuronal compartments for sub-cellular and molecular studies. Moreover, the design of the central chamber enables to expose the synapses to chemicals or other cells types like astrocytes or microglia to study their effects on a specific class of synapses. We will produce a convenient kit with the frozen human neurons, the microfluidic chamber and a detailed protocol for generating the patterned neuronal circuits for research studies, compound testing and toxicology research.

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Topic(s)

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Funding Scheme

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ERC-POC - Proof of Concept Grant

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Call for proposal

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(opens in new window) ERC-2018-PoC

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Host institution

OSPEDALE SAN RAFFAELE SRL
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 100 000,00
Address
VIA OLGETTINA 60
20132 Milano
Italy

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Region
Nord-Ovest Lombardia Milano
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 100 000,00

Beneficiaries (2)

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