Studying patient specific cardiac diseases (CD) requires disease models that can recapitulate particular phenotypes. The use of human induced pluripotent stem cell (hiPSC) derived cardiomyocytes (hiPSC-CMs) has become an important tool to model CDs, since the reprogramming of patient cells into hiPSCs is possible. Furthermore, since hiPSCs are obtained from humans, the interspecies differences are minimized. hiPSC-CMs have been used over the years to model various CDs, such as arrhythmogenic cardiomyopathy, dilated cardiomyopathy, and Duchenne muscular dystrophy, to name a few. Subsequently, hiPSC-CMs are used for drug screening since this model is closer to humans. Although this model is widely used and holds many promises, one of the major shortcomings of hiPSC-CMs is their immaturity where they are more fetal-like in terms of their electrophysiology, metabolism, and/or structure.
Nevertheless, the 2D culture of hiPSC-CMs can be used to create 3-dimensional engineered heart tissues (EHT) that have shown to have improved electrophysiological, structural, and metabolic properties. Since EHTs have more mature phenotypes, similar to adult cardiomyocytes, their use is increasingly gaining popularity, and they are proving to be an important tool for CD modeling.
Within the scope of this grant, ring-shaped EHTs will be generated from control hiPSC-CMs. Several properties of these EHTs will be evaluated, including presence of cardiac markers and the structural organization of cardiomyocytes. The successful generation of control EHTs will allow for their use to model patient-specific mutations using patient derived hiPSC-CMs harboring different CDs. Finally, the future aim will be to use these tissues for testing of specific drugs in different disease models.