Coming of age of human stem cell derived cardiomyocytes : towards functional maturation of human pluripotent stem cell derived cardiomyocytes and their use in understanding inherited arrhythmia syndromes

Kosmidis, G. (2017)

Doctoral Thesis

The focus of this thesis is about cardiomyocytes derived from human pluripotent stem cells (hPSC-CMs). hPSC-CMs are an established model used to study cardiac diseases as well as a good tool for drug efficacy and cardiotoxicity studies.
The core aspect of the thesis is about hPSC-CMs derived from patients carrying genetic mutations that result in a cardiac arrhythmia known as Brugada syndrome. With these cells we manage to model the disease in vitro at the cellular level and assess the impact of specific drugs (readthrough-promoting) in an attempt to provide a valuable clinical perspective. The use of novel genetic engineering techniques (CRISPR-Cas9) helped us to further understand the link between the genotype of the patients and the phenotype of the disease. Furthermore the thesis contains our research attempts to improve hPSC-CMs so that they resemble more to adult human cardiomyocytes, since this would increase the validity of this model system and help us understand the nature of even more cardiac diseases.

• Cardiomyocytes
• Stem cells
• Induced pluripotent
• Arrhythmias
• Cardiac maturation
• Readthough promoting

• All authors: Kosmidis, G.
• Editor(s): Kosmidis G.
• Supervisor: Mummery, C.L.
• Co-supervisor: Bellin, M.; Casini, S.
• Committee: Goumans, M.-J.; Atsma, D.E.; Bezzina, C.R.; Passier, R.
• Qualification: Doctor (dr.)
• Awarding Institution: Medicine, Leiden University
• Date: 2017-10-11
• ISBN (print): 9789462956957