Lack of Laminin γ1 in Embryonic Stem Cell-Derived Cardiomyocytes Causes Inhomogeneous Electrical Spreading Despite Intact Differentiation and Function

doi:10.1634/stemcells.2008-0335

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Wiley InterScience

STEM CELLS

Volume 27 Issue 1, Pages 88 - 99

Published Online: 5 Jan 2009

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Embryonic Stem Cells/Induced Pluripotent Stem Cells

Lack of Laminin

1 in Embryonic Stem Cell-Derived Cardiomyocytes Causes Inhomogeneous Electrical Spreading Despite Intact Differentiation and Function^§

Daniela Malan^{1 2}, Michael Reppel³, Radoslaw Dobrowolski⁴, Wilhelm Roell^{1 5}, Neil Smyth^{6 7}, Juergen Hescheler³, Mats Paulsson⁶, Wilhelm Bloch^{2 *}^¶, Bernd K. Fleischmann^{1 *}^||

¹Institute of Physiology I, Life and Brain Center, University of Bonn, Bonn, Germany
²Department of Molecular and Cellular Sport Medicine, German Sport University, Cologne, Germany
³Institute of Neurophysiology, University of Cologne, Cologne, Germany
⁴Institute of Genetics, University of Bonn, Bonn, Germany
⁵Department of Cardiac Surgery, University of Bonn, Bonn, Germany
⁶Center for Biochemistry, Medical Faculty and Center for Molecular Medicine, University of Cologne, Cologne, Germany
⁷School of Biological Sciences, University of Southampton, Southampton, United Kingdom

email: Wilhelm Bloch (w.bloch@dshs-koeln.de) Bernd K. Fleischmann (bernd.fleischmann@uni-bonn.de)

^*Correspondence to Wilhelm Bloch, Department of Molecular and Cellular Sport Medicine, German Sport University Cologne, Carl-Diem-Weg 6, 50927 Cologne, Germany

^*Correspondence to Bernd K. Fleischmann, Institute of Physiology I, Life & Brain Center, University of Bonn, Sigmund-Freud-Strasse 25, 53105 Bonn, Germany

Author contributions: D.M.: collection of data, data analysis and interpretation, manuscript writing; M.R., R.D., and W.R.: collection of data, data analysis and interpretation; N.S.: provision of study material, collection of data, data analysis and interpretation; J.H.: data interpretation; M.P.: provision of study material, data interpretation; W.B. and B.K.F.: conception and design, data interpretation, financial support, manuscript writing, final approval of the manuscript.
Disclosure of potential conflicts of interest is found at the end of this article.
^§First published online in STEM CELLS Express October 16, 2008.
^¶Telephone: 49-221-4982-5380; Fax: 49-221-4982-8370
^||Telephone: 49-228-6885-200; Fax: 49-228-6885-201

Funded by:
Deutsche Forschungsgemeinschaft; Grant Number: BL 419/2-2, SM 65/1-3 within Priority Program 1086, SFB 645, B2

Keywords

Laminin

1 • Extracellular matrix • Embryonic stem-derived cardiomyocytes • Hormonal regulation

Abstract

Laminins form a large family of extracellular matrix (ECM) proteins, and their expression is a prerequisite for normal embryonic development. Herein we investigated the role of the laminin

1 chain for cardiac muscle differentiation and function using cardiomyocytes derived from embryonic stem cells deficient in the LAMC1 gene. Laminin

1 (-/-) cardiomyocytes lacked basement membranes (BM), whereas their sarcomeric organization was unaffected. Accordingly, electrical activity and hormonal regulation were found to be intact. However, the inadequate BM formation led to an increase of ECM deposits between adjacent cardiomyocytes, and this resulted in defects of the electrical signal propagation. Furthermore, we also found an increase in the number of pacemaker areas. Thus, although laminin and intact BM are not essential for cardiomyocyte development and differentiation per se, they are required for the normal deposition of matrix molecules and critical for intact electrical signal propagation. STEM CELLS 2009;27:88-99

Received: 2 April 2008; Accepted: 3 October 2008

Digital Object Identifier (DOI)

10.1634/stemcells.2008-0335 About DOI