| Project Detail |
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 Sklodowska-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 hearts 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.
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 labs 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. |
