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Embryonic Stem Cells/Induced Pluripotent Stem Cells
Article first published online: 5 JAN 2009
Copyright © 2008 AlphaMed Press
Volume 27, Issue 1, pages 88–99, January 2009
How to Cite
Malan, D., Reppel, M., Dobrowolski, R., Roell, W., Smyth, N., Hescheler, J., Paulsson, M., Bloch, W. and Fleischmann, B. K. (2009), Lack of Laminin γ1 in Embryonic Stem Cell-Derived Cardiomyocytes Causes Inhomogeneous Electrical Spreading Despite Intact Differentiation and Function. STEM CELLS, 27: 88–99. doi: 10.1634/stemcells.2008-0335
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 CELLSExpress October 16, 2008.
- Issue published online: 5 JAN 2009
- Article first published online: 5 JAN 2009
- Manuscript Accepted: 3 OCT 2008
- Manuscript Received: 2 APR 2008
- Deutsche Forschungsgemeinschaft. Grant Numbers: BL 419/2-2, SM 65/1-3 within Priority Program 1086, SFB 645, B2
- Laminin γ1;
- Extracellular matrix;
- Embryonic stem-derived cardiomyocytes;
- Hormonal regulation
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 γ1 chain for cardiac muscle differentiation and function using cardiomyocytes derived from embryonic stem cells deficient in the LAMC1 gene. Laminin γ1 (−/−) 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 CELLS2009;27:88–99