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Stem Cells International
Volume 2017, Article ID 4651238, 17 pages
https://doi.org/10.1155/2017/4651238
Research Article

Activin A Modulates CRIPTO-1/HNF4α+ Cells to Guide Cardiac Differentiation from Human Embryonic Stem Cells

1Translational Cardiomyology Laboratory, Stem Cell Biology and Embryology Unit, Department of Development and Regeneration, KU Leuven, 3000 Leuven, Belgium
2Experimental Cardiology, Department of Cardiovascular Sciences, KU Leuven, 3000 Leuven, Belgium
3Stem Cell Institute Leuven and Stem Cell Biology and Embryology Unit, Department of Development and Regeneration, KU Leuven, 3000 Leuven, Belgium
4Child Neurology, University Hospitals Leuven, Department of Development and Regeneration, KU Leuven, 3000 Leuven, Belgium
5Tissue Engineering Laboratory, Department of Development and Regeneration, KU Leuven, Campus Kulak Kortrijk, 8500 Kortrijk, Belgium
6Division of Human Anatomy, Department of Public Health, Experimental and Forensic Medicine, University of Pavia, 27100 Pavia, Italy

Correspondence should be addressed to Maurilio Sampaolesi; eb.nevueluk.dem@iseloapmas.oiliruam

Received 5 August 2016; Revised 29 October 2016; Accepted 1 December 2016; Published 9 January 2017

Academic Editor: Leonard M. Eisenberg

Copyright © 2017 Robin Duelen et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The use of human pluripotent stem cells in basic and translational cardiac research requires efficient differentiation protocols towards cardiomyocytes. In vitro differentiation yields heterogeneous populations of ventricular-, atrial-, and nodal-like cells hindering their potential applications in regenerative therapies. We described the effect of the growth factor Activin A during early human embryonic stem cell fate determination in cardiac differentiation. Addition of high levels of Activin A during embryoid body cardiac differentiation augmented the generation of endoderm derivatives, which in turn promoted cardiomyocyte differentiation. Moreover, a dose-dependent increase in the coreceptor expression of the TGF-β superfamily member CRIPTO-1 was observed in response to Activin A. We hypothesized that interactions between cells derived from meso- and endodermal lineages in embryoid bodies contributed to improved cell maturation in early stages of cardiac differentiation, improving the beating frequency and the percentage of contracting embryoid bodies. Activin A did not seem to affect the properties of cardiomyocytes at later stages of differentiation, measuring action potentials, and intracellular Ca2+ dynamics. These findings are relevant for improving our understanding on human heart development, and the proposed protocol could be further explored to obtain cardiomyocytes with functional phenotypes, similar to those observed in adult cardiac myocytes.