Project description
3D model for cardiovascular disease drug screening
Reliable 3D disease models are essential for accurately mimicking the complex interactions and structures of human tissues in various diseases. These models enhance the understanding of disease mechanisms and improve the testing and development of effective treatments, bridging the gap between preclinical studies and clinical applications. Funded by the Marie Skłodowska-Curie Actions programme, the CARDINAL project aims to develop a 3D heart model using human induced pluripotent stem cells. Using innovative scaffolds, researchers will replicate the heart's muscle structure and contractility, which is crucial for efficient function. This model will improve drug screening for cardiovascular diseases, the leading cause of death globally.
Objective
Cardiovascular diseases (CVDs) are the leading cause of death worldwide. Chronic treatments of CVDs are scarce because of poor predictivity of current two-dimensional (2D) pre-clinical models. State-of-the-art 3D-tissue models based on human induced pluripotent stem cells (hiPSCs) can be more predictive of human genetics but fail to replicate the 3D cardiac muscle structure. In fact, the heart evolved to ensure efficient emptying of the chambers via a 3D chiral organization of muscle tissue not yet recapitulated in organoids or engineered ventricles.
In CARdiac tissue Design, beating INduction, and Assessment using multiwavelength Light (CARDINAL), I will replicate the native chiral architecture of the heart in a minimal 3D model of the heart muscle and validate the resulting assay for drug screening.
Our objectives will tackle three main challenges in the field:
1) Create the chiral scaffold to host the hiPSC-derived cardiac muscle cells (hiPSC-CMs). I will use cavitation molding - a light-based 3D-structuring method I previously developed - to obtain chirally organized micro-channels in soft hydrogels.
2) Populate these scaffolds with high-purity hiPSC-CMs that can be triggered and assayed with optical methods. I will leverage the host lab's engineered hiPSC line that features structural and functional fluorescent sensors. To that line, we will add optogenetic actuators and antibiotic resistance to directly control the final hiPSC-CM yield, trigger contraction, and image cell structure and function volumetrically.
3) Validate the predictivity of our new 3D chiral platform in drug screening applications. To do that, we will test a panel of cardiac drugs with known safety/efficacy profiles with our new platform, 2D hydrogels, and traditional glass slides.
The CARDINAL project will provide the drug screening field with a more biomimetic tissue-engineered model of the heart muscle that can be extended to vascularized models and the full organ, eventually.
Fields of science (EuroSciVoc)
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CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- engineering and technology electrical engineering, electronic engineering, information engineering electronic engineering sensors
- engineering and technology materials engineering amorphous solids
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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Topic(s)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) HORIZON-MSCA-2023-PF-01
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27100 Pavia
Italy
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