title: Tissue-Mimicking Geometrical Constraints Stimulate Tissue-Like Constitution and Activity of Mouse Neonatal and Human-Induced Pluripotent Stem Cell-Derived Cardiac Myocytes.
abstract: 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.
authors.affiliation: Kirchhoff Institute für Physik, Im Neuenheimer Feld INF 270, Heidelberg D-69120, Germany. goetz.pilarczyk@kip.uni-heidelberg.de.
authors.forename: Götz
authors.initials: G
authors.lastname: Pilarczyk
authors.affiliation: Institut für Physiologie der Unversität Bonn, Life &amp; Brain Center, Sigmund Freud Strasse 25, Bonn D-53127, Germany. araulf@uni-bonn.de.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Raulf
authors.affiliation: ViroQuant Cell Networks RNAi Screening Facility, BioQuant Center, Im Neuenheimer Feld INF 267, Heidelberg D-69120, Germany. manuel.gunkel@bioquant.uni-heidelberg.de.
authors.forename: Manuel
authors.initials: M
authors.lastname: Gunkel
authors.affiliation: Institut für Physiologie der Unversität Bonn, Life &amp; Brain Center, Sigmund Freud Strasse 25, Bonn D-53127, Germany. Bernd.Fleischmann@uni-bonn.de.
authors.forename: Bernd K
authors.initials: BK
authors.lastname: Fleischmann
authors.affiliation: Luxembourg Institute for Science and Technology, 5 avenue des Hauts-Fourneaux, Esch-Belval L-4362, Luxembourg. robert.lemor@list.lu.
authors.forename: Robert
authors.initials: R
authors.lastname: Lemor
authors.affiliation: Kirchhoff Institute für Physik, Im Neuenheimer Feld INF 270, Heidelberg D-69120, Germany. hausmann@kip.uni-heidelberg.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Hausmann
keywords: cardiac tissue engineering; hIPSC-derived cardiac myocytes; stem cells; structure-based cardiac arrhythmia; surface pattern