Project

Research on cardiomyopathies using models derived from human stem cells

Code
bof/baf/4y/2024/01/725
Duration
01 January 2024 → 31 December 2025
Funding
Regional and community funding: Special Research Fund
Research disciplines
  • Natural sciences
    • Cell signalling
    • Cellular interactions and extracellular matrix
    • Cytoskeleton
    • Molecular and cell biology not elsewhere classified
  • Medical and health sciences
    • Cardiology
    • Cytoskeleton
    • Tissue engineering
    • Biomechanics
Keywords
stem cells Transmission electron microscopy Arrhythmogenic cardiomyopathy cell adhesion induced pluripotent stem cells Marfan syndrom Extracellular Matrix
 
Project description

The research line of the Medical Cell Biology group is at the interface between stem cells, regenerative medicine and cardiology. Currently, the main focus is on Marfan's cardiomyopathy and arrhythmogenic cardiomyopathy (ACM), both analysed in 2D/3D human induced pluripotent stem cell-derived models. The cardiomyopathy models require in-depth functional characterisation to gain insight into their underlying mechanisms.

Marfan syndrome is a systemic disorder caused by defects in the matrix protein fibrillin-1. Accumulating evidence suggests that Marfan syndrome causes a primary cardiomyopathy. Importantly, the cardiac stroma, composed of cardiac fibroblasts, is increasingly recognised as an active player in cardiac development, repair and disease. ACM is a genetic heart muscle disorder that can lead to abnormal heart rhythm and sudden cardiac death. The aim is to use CRISPRi screens to identify novel genes and therapeutic targets for Marfan and ACM.

A new research line creates a jump on the state-of-the-art by launching the plasma-assisted development of an innovative heart patch encompassing three biomimetic layers having distinctive topographical and biochemical cues: 1) mechanical support layer, 2) vascularization[1]promoting layer and 3) contractile layer with integrated biodegradable and stretchable multi-electrode array. Fibroblasts, endothelial cells and cardiomyocytes will be cultured under electro-mechanical stimulation on the corresponding layers that will be combined to generate an all-in-one pre-vascularized, contractile and mechanically compatible heart patch.