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Project

A Deaf Heart Promotes Proliferation: Using iPSC-Based 3D Models to Study Mitogenic Cardiomyopathy in Alström Syndrome.

In the current project, we aim at generating 3D human engineered heart tissues (EHTs) as unprecedented in vitro disease model to study novel molecular mechanistic insights on the pathogenesis of Alström Syndrome (ALMS)-associated cardiomyopathy (mitogenic cardiomyopathy). The 3D EHT constructs will be generated by embedding induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) in synthetic hydrogel, functionalized with cardiac-specific peptides that support robust differentiation and maturation. The strength lies on the tunability of the 3D system - mimicking the extracellular matrix (ECM) composition as reported in ALMS hearts - allowing us to investigate the role of the proliferation-associated WNT and YAP/TAZ signaling pathways in ALMS onset and progression.Our knowledge about the disease mechanisms resulting in mitogenic cardiomyopathy, could lead in long-term to the identification of new molecular targets for therapeutic interventions. The platform will also enable pharmacological drug screening and development (both efficacy and toxicity), and can be extended to other non-ALMS related cardiomyopathy. This further broadens the translational and clinical potential and impact, since animal models do not fully recapitulate the human disease. Lastly, a promising future application of the patient-specific iPSC-based disease model allows the concept of personalized medicine.
Date:1 Oct 2021 →  30 Sep 2022
Keywords:Human Induced Pluripotent, Stem Cells, 3D Tissue Engineering, Alström Cardiomyopathic Disease Modeling
Disciplines:Tissue engineering, Cardiology, Stem cell biology, Molecular and cell biology not elsewhere classified