The project will use patient derived-iPSC and CRISPR-edited human IPSC to develop a novel three-dimensional microfluidic system for drug discovery.
Start – End dates: 01/12/22 – 30/11/25
Project reference: PLEC2022-009341
Total budget: 685,474.81€
Financed by: Ministry of Science and Innovation of Spain, NextGenerationEU,
Financed by MCIN/AEI/10.13039/501100011033 European Union-NextGenerationEU/PRTR.
Partners: Universitat de Barcelona
Summary:
The current research framework makes it mandatory to develop appropriate methodologies that permit the replacement of animals (NAMs) while modeling with accuracy human biological processes disturbed in disease. Organoids, in vitro 3D cellular assemblies resembling human organs, are promised to be the new research paradigm to solve animal replacement and enhance preclinical predictivity. Among those, neural organoids have the capability to mimic brain structures and functions, including neural connectivity. Interestingly, neural organoid networks display asynchronous behaviors when cells are mutated for genes associated with neuropsychiatric diseases, specifically schizophrenia. This asynchronous behavior can be solved by the administration of standard-of-care drugs.
ZeClinics, the coordinator of this proposal, led by Dr. Rabadan, the developer of this technology, has joined forces with the SIC-BIO research group at the University of Barcelona, experts in microphysiological platforms development using microfluidic technology. The aim of the proposal is to redesign the neural organoid generation strategy using human iPSC-derived neurons as the basis for conforming organoids and building a microfluidic chip that controls the size and network conformation. The expectation is that the resulting solution (ZeNeuroid) will provide an excellent research tool for modeling neuropsychiatric diseases, with relevant human translatability.
For this aim, we will use patient derived-iPSC and CRISPR-edited human iPSC for neuronal disease models to develop a novel three-dimensional microfluidic system that combines sophisticated cell culture with biomedical engineering to study complex neuronal processes in the disease model, but also to test therapeutic targets and pharmacological molecules in these non-invasive and animal-free model in a more efficient way.