Quantifying functional phenotypes in human pluripotent stem cell derived cardiomyocytes for disease modelling and drug discovery

Meer, B.J. van

Studying diseases or effects of new drugs on the human body is challenging, not least because of the lack of proper testing models that recapitulate human physiology. Most research is done using animal models but these often show differences with humans in disease manifestation and responses to drugs. For example, drugs that had no effect on the hearts of animals later turned out to cause lethal arrhythmias in some humans. This – and the ethical issues around animal testing – is why, as in this thesis, there is increasing interest on making human heart models based on pluripotent stem cells (hPSCs). Nowadays small numbers of cells can be collected from a patient (e.g. from blood, urine or skin), reprogrammed to hiPSCs, and then differentiated to heart muscle cells (cardiomyocytes). Since the genetics of the patient are maintained during reprogramming, the phenotype of a genetic disease affecting cardiac function can also be captured. The focus of this thesis has been developing...Show moreStudying diseases or effects of new drugs on the human body is challenging, not least because of the lack of proper testing models that recapitulate human physiology. Most research is done using animal models but these often show differences with humans in disease manifestation and responses to drugs. For example, drugs that had no effect on the hearts of animals later turned out to cause lethal arrhythmias in some humans. This – and the ethical issues around animal testing – is why, as in this thesis, there is increasing interest on making human heart models based on pluripotent stem cells (hPSCs). Nowadays small numbers of cells can be collected from a patient (e.g. from blood, urine or skin), reprogrammed to hiPSCs, and then differentiated to heart muscle cells (cardiomyocytes). Since the genetics of the patient are maintained during reprogramming, the phenotype of a genetic disease affecting cardiac function can also be captured. The focus of this thesis has been developing methods to measure these cardiac phenotypes robustly and with sufficient complexity to reflects drug responses and disease of the heart. Our results supported the notion that hPSC models will become human avatars and accurate measurement models able to recapitulate essential human-specific processes.Show less

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Quantifying functional phenotypes in human pluripotent stem cell derived cardiomyocytes for disease modelling and drug discovery

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