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Tissue-Mimicking Geometrical Constraints Stimulate Tissue-Like Constitution and Activity of Mouse Neonatal and Human-Induced Pluripotent Stem Cell-Derived Cardiac Myocytes

1
Kirchhoff Institute für Physik, Im Neuenheimer Feld INF 270, Heidelberg D-69120, Germany
2
Institut für Physiologie der Unversität Bonn, Life & Brain Center, Sigmund Freud Strasse 25, Bonn D-53127, Germany
3
ViroQuant Cell Networks RNAi Screening Facility, BioQuant Center, Im Neuenheimer Feld INF 267, Heidelberg D-69120, Germany
4
Luxembourg Institute for Science and Technology, 5 avenue des Hauts-Fourneaux, Esch-Belval L-4362, Luxembourg
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Francesco Puoci
J. Funct. Biomater. 2016, 7(1), 1; https://doi.org/10.3390/jfb7010001
Received: 27 October 2015 / Revised: 17 December 2015 / Accepted: 18 December 2015 / Published: 7 January 2016
The present work addresses the question of to what extent a geometrical support acts as a physiological determining template in the setup of artificial cardiac tissue. Surface patterns with alternating concave to convex transitions of cell size dimensions were used to organize and orientate human-induced pluripotent stem cell (hIPSC)-derived cardiac myocytes and mouse neonatal cardiac myocytes. The shape of the cells, as well as the organization of the contractile apparatus recapitulates the anisotropic line pattern geometry being derived from tissue geometry motives. The intracellular organization of the contractile apparatus and the cell coupling via gap junctions of cell assemblies growing in a random or organized pattern were examined. Cell spatial and temporal coordinated excitation and contraction has been compared on plain and patterned substrates. While the α-actinin cytoskeletal organization is comparable to terminally-developed native ventricular tissue, connexin-43 expression does not recapitulate gap junction distribution of heart muscle tissue. However, coordinated contractions could be observed. The results of tissue-like cell ensemble organization open new insights into geometry-dependent cell organization, the cultivation of artificial heart tissue from stem cells and the anisotropy-dependent activity of therapeutic compounds. View Full-Text
Keywords: hIPSC-derived cardiac myocytes; surface pattern; cardiac tissue engineering; stem cells; structure-based cardiac arrhythmia hIPSC-derived cardiac myocytes; surface pattern; cardiac tissue engineering; stem cells; structure-based cardiac arrhythmia
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MDPI and ACS Style

Pilarczyk, G.; Raulf, A.; Gunkel, M.; Fleischmann, B.K.; Lemor, R.; Hausmann, M. Tissue-Mimicking Geometrical Constraints Stimulate Tissue-Like Constitution and Activity of Mouse Neonatal and Human-Induced Pluripotent Stem Cell-Derived Cardiac Myocytes. J. Funct. Biomater. 2016, 7, 1.

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