Cardiomyocytes, the working muscle cells of the heart, are terminally differentiated cells in the adult organism and regeneration is limited. This is a worrisome fact, since ischemia and cardiotoxic compounds can lead to cell death and irreversible decline of cardiac function. Our group is investigating the cardiotoxicity of old and new cancer therapies on the heart and survival pathways that exist in the organ.
As in vitro model, isolated organs and primary cells from rodents have been the standard in research and toxicology so far, but there is a need for better models. Therefore, we are developing a model comprising both the advantages of scaffold-free 3D cell culture and cardiomyocytes derived from induced pluripotent stem cells (iPSC) of human origin. Myocardial microtissues (MT) are generated by self-assembly in multi-well hanging drop cultures. In the hanging drop cultures, iPSC-derived cardiomyocytes formed MT’s within 4 days, and those were contracting up to 3 weeks and recorded by optical motion tracking. Morphological and functional characterization underline that this model might become a valuable tool for research on the mechanisms of cardiotoxicity of cancer therapies in the future