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ORIGINAL RESEARCH ARTICLE

Molecular and Pharmacological Properties of Human Embryonic Stem Cell–Derived Cardiomyocytes

Anders Norström^*, Karolina Åkesson, Thorir Hardarson, Lars Hamberger^*, Petter Björquist and Peter Sartipy^,1

^* Department of Obstetrics and Gynecology, Sahlgrenska University Hospital, SE-413 45 Göteborg, Sweden; Cellartis AB, Arvid Wallgrens Backe 20, SE- 413 46 Göteborg, Sweden; and Fertility Center, Carlandersplatsen, SE-402 29 Göteborg, Sweden

To whom requests for reprints should be addressed at ¹ Cellartis AB, Arvid Wallgrens Backe 20, SE-413 46 Göteborg, Sweden. E-mail: peter.sartipy{at}cellartis.com

Human embryonic stem cells (hESCs) can be coaxed to differentiate into specific cell types, including cardiomyocyte-like cells. These cells express cardiac-specific markers and display functional similarities to their adult counterparts. Based on these properties, hESC-derived cardiomyocytes have the potential to be extremely useful in various in vitro applications and to provide the opportunity for cardiac cell replacement therapies. However, before this can become a reality, the molecular and functional characteristics of these cells need to be investigated in more detail. In the present study we differentiate hESCs into cardiomyocyte-like cells via embryoid bodies (EBs). The fraction of spontaneously beating clusters obtained from the EBs averaged approximately 30% of the total number of EBs used. These cell clusters were isolated, dissociated into single-cell suspensions, and frozen for long-term storage. The cryopreserved cells could be successfully thawed and subcultured. Using electron microscopy, we observed Z discs and tight junctions in the hESC-derived cardiomyocytes, and by immunohistochemical analysis we detected expression of cardiac-specific markers (cTnI and cMHC). Notably, using BrdU labeling we also could demonstrate that some of the hESC-derived cardiomyocytes retain a proliferative capacity. Furthermore, pharmacological stimulation of the cells resulted in responses indicative of functional adrenergic and muscarinic receptor coupling systems. Taken together, these results lend support to the notion that hESCs can be used as a source for the procurement of cardiomyocytes for in vitro and in vivo applications.

Key Words: stem cells • differentiation • myocytes

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				J. Synnergren, K. Akesson, K. Dahlenborg, H. Vidarsson, C. Ameen, D. Steel, A. Lindahl, B. Olsson, and P. Sartipy Molecular Signature of Cardiomyocyte Clusters Derived from Human Embryonic Stem Cells Stem Cells, July 1, 2008; 26(7): 1831 - 1840. [Abstract] [Full Text] [PDF]