Human Pluripotent Stem Cell -Derived Cardiomyocytes
Differentiation, Analysis & Disease Modeling



By Ville Kujala
April 2012
Tampere University Press
Distributed by Coronet Books Inc.

ISBN: 9789514487453
167 pages

$82.50 Paper original



Stem cell technology is an area of research that will hopefully bring new treatment options to the currently available traditional medical therapies, drug therapies and surgeries. In particular, this field brings hope of new disease and drug testing models and the potential for human spare parts. New disease models would allow for the more accurate study of major illnesses at the cellular and tissue level using cells of human origin. Pharmaceutical testing models could, in turn, provide more detailed information on the pharmacodynamic effects of medicines that are not able to be investigated using current cellular and animal models. A particularly important application area of stem cell technology are the heart muscle cells (cardiomyocytes) for which there has been no human cell model, as genetic heart diseases can be fatal and because a large number of drugs cause serious cardiac side effects. Pluripotent stem cell-derived cardiomyocytes bring hope to these medical challenges.

This thesis describes the differentiation of human pluripotent stem cells into cardiomyocytes. The molecular biology of these cardiomyocytes was analyzed using several methods. The electrophysiological properties of these cells were recorded with a microelectrode array (MEA) platform, in addition to other methods, and analyzed using in-house developed software. The responses of the cardiomyocytes to various drugs were also studied using the MEA platform. Using hiPSC technology, we investigated the properties of a genetic cardiac disease, the long QT syndrome, in human cells. This research demonstrates that human pluripotent stem cells can differentiate towards multiple cell lineages, including functional cardiomyocytes, which have spontaneous beating activity. Moreover, these cells express cardiac-specific markers, exhibit the typical electrophysiological profiles of cardiomyocytes, and respond to different pharmacological substances in a way that is characteristic of cardiomyocytes. The electrophysiological properties that were recorded with the MEA platform were robustly analyzed for different cardiac parametes using software that we developed. Correct phenotypic characteristics of the long QT syndrome could also be recapitulated in the laboratory, paving way for more in-depth future studies.

 

Acta Universitatis TamperensisNo. 1710

 

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