Cardiomyocyte Differentiation from Human Pluripotent Stem Cells

Acta Universitatis Tamperensis, No. 1555


By Mari Pekkanen-Mattil
November 2010
Tampere University Press
Distributed by Coronet Books
ISBN: 9789514482342
162 pages
$77.50 Paper Original

The rapid development of stem cell technology has raised hopes for new and even revolutionary treatments for cardiac and other disorders with tissue damage. The adult human heart has very limited capability to regenerate and undergo extensive repair which is needed, for example, after myocardial infarction. Pluripotent stem cells, human embryonic stem cells (hESC) and human induced pluripotent stem (iPS) cells can be differentiated into cardiomyocytes by multiple methods. In spite of this development, therapeutic use of stem cell-derived cardiomyocytes is in its infancy.

However, functional cardiomyocytes can be differentiated from stem cells and they are themselves very useful as a cardiac cell model. Development of human iPS technology has raised the hope for the potential use of differentiated cardiomyocytes even further. By this method, patient specific stem cell lines can be derived and therefore disease models for genetic illnesses can be obtained.

The present thesis describes the differentiation of cardiomyocytes from pluripotent stem cells. The differentiation potential of several hESC lines and iPS cells was evaluated and the differentiated cells were characterized. Furthermore, the differentiation potential of hESC and iPS cells cultured on mouse and human feeder cells was monitored. Differentiation was performed by two differentiation methods, spontaneously in embroid bodies (EBs) and in co-culture with mouse visceral-endoderm-like cells (END-2 cells). In addition to the cardiac aspect, the formation of EBs and the differentiation of germ layers were evaluated in general. Differentiated cells were characterized by multiple molecular biology methods and their electrophysiological properties were also determined.

Pluripotent stem cells can be differentiated into functional cardiomyocytes even though the differentiation efficiency is low and cell lines differ in their cardiac differentiation potential. The differentiated cells beat spontaneously and expressed specific cardiac markers. The populations of the differentiated cardiomyocytes were heterogenous, containing mainly ventricular cardiomyocytes with varying maturation states. However, some of the differentiated cells had relatively mature characteristics, resembling adult human cardiac phenotype.

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