Human iPS cell based myocardial tissue as model of heart failure and cardiac assist device therapy: molecular characterization and identification of therapeutic strategies

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In TP5 we aim to establish an in vitro model of the failing myocardium and cardiac ventricular assist device therapy, in order to dissect molecular mechanisms of cardiac unloading in bioarticifial cardiac tissue (BCT) and to identify and test novel additive therapeutic approaches. For example, we will examine whether the anti-androgenic substance Finasteride, which according to our recent work exerts antihypertrophic and antifibrotic effects in the mouse myocardium, is able to improve the pathological changes of the failing BCT heart tissue when administered in addition to physical unloading. In a similar manner, we will analyze the impact of downregulating the prohypertrophic protein CIB1 or overexpression of the anti-hypertrophic protein TIP30. The BCTs will be generated from human iPS cells (from healthy donors as well as from patients with genetic cardiomyopathy) after their differentiation into cardiac myocytes. The BCTs will be subjected to controlled over-stretching, subsequent unloading and detailed functional, histological and molecular characterization.