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Organoids For Heartbreak

Project description

A breakthrough in cardiac fibrosis research

Cardiac fibrosis is a leading cause of heart failure. The condition arises from an imbalance in the interplay between endothelial cells, cardiomyocytes, and cardiac fibroblasts, contributing to tissue scarring and impaired heart function. Current models fail to fully capture the complexity of this process, while animal models raise ethical concerns. Supported by the Marie Skłodowska-Curie Actions programme, the OrganoidsFHeartbreak project aims to develop a cardiac organoid-on-chip platform for disease modelling and drug testing. It will enable the identification of molecular mechanisms behind cardiac fibrosis, particularly focusing on the Renin-Angiotensin-Aldosterone System. It will also evaluate the impact of known medications. Overall, the project paves the way for the replacement of animal models in both mechanistic research and drug development.

Objective

This project is a proof-of-concept study for organoid drug testing platform for disease modeling of cardiac fibrosis. I am going to develop a cardiac organoid on chip platform for disease modeling of cardiac fibrosis to identify the molecular mechanism of the pathologic interplay between endothelial cells, cardiomyocytes and cardiac fibroblasts, and its regulation by specific drug treatments. This model will be based on cardiac organoids previously developed at the host lab modified with endothelial cell component. Organoids with and without endothelial cells will be a tool for identification of endothelial contribution in cardiac fibrosis. Molecular mechanisms will be identified through selective interventions in known fibrotic pathways, with special focus on the Renin-Angiotensin-Aldosterone System. In addition, validity of this tool for drug testing will be established by proof-of-effect of known medications on fibrotic molecular phenotype and cardiac function. The platform will be designed as medium through-put for patient treatment optimization (precision medicine) and drug testing. Collectively, it has the potential to replace animal models in mechanistic research and drug development.

The host lab is the perfect fit for this project. It has been on the forefront of cardiac organoid research and their previous work is the cornerstone for the cardiac organoid model used here. They possess the latest equipment for on-chip organoid cultivation and have extensive experience with augmentation and optimization of biopolymer hardness to simulate fibrotic environment. Additionally, Prof. Sluijter’s professional network of contacts and cooperation with local university spin-off companies provides the opportunity to investigate the interest of the industry in application of this project by scale-up of our drug testing platform for high through-put organoid drug screening platform.

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Topic(s)

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2022-PF-01

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Coordinator

UNIVERSITAIR MEDISCH CENTRUM UTRECHT
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.

€ 187 624,32
Address
HEIDELBERGLAAN 100
3584 CX Utrecht
Netherlands

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Activity type
Higher or Secondary Education Establishments
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Total cost

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