Mimicking heart disease in a dish: Cardiac disease modelling through functional analysis of human stem cell derived cardiomyocytes

Heart failure renders the heart unable to pump enough blood through the body. Despite advances in its treatment the quality of life with heart failure remains poor and half of the patients passes away within five years of the diagnosis. Additionally, heart failure affects one out of fifty adults, therefore the need for new treatments is critical. However, it is very challenging to develop new treatments for heart failure because we do not yet fully understand how heart failure develops. In this thesis we have performed research with human stem cells that were cultured to become heart cells after which they start beating in a lab dish. We then simulated several causes of heart failure in the lab to study the responses of these heart cells. In order to perform this research, we first developed a new method that allowed us to more precisely measure the force and speed of the contractions of heart cells. Because iron deficiency results in worse outcomes for patients with heart failure, we then induced iron deficiency in these heart cells and analyzed the effect. Next, we researched the effect of chemotherapy on the heart cells to determine why chemotherapy reduces the contractile function of the heart. The research described in this thesis has provided us with new insights into the effects of iron deficiency and chemotherapy on the human heart. We hope that our methods and the resulting research will contribute to a better treatment for patients with heart failure in the future.