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Stem Cells International
Volume 2016, Article ID 2936126, 12 pages
http://dx.doi.org/10.1155/2016/2936126
Research Article

The Interaction between Adult Cardiac Fibroblasts and Embryonic Stem Cell-Derived Cardiomyocytes Leads to Proarrhythmic Changes in In Vitro Cocultures

1Department of Paediatric Cardiology, Heart Centre Cologne, University Hospital of Cologne, Kerpener Strasse 62, 50937 Cologne, Germany
2Institute for Neurophysiology, University of Cologne, Robert-Koch-Strasse 39, 50931 Cologne, Germany
3Department of Paediatrics, University Hospital of Cologne, Kerpener Strasse 62, 50937 Cologne, Germany
4Department of Internal Medicine III, Heart Centre Cologne, University of Cologne, Kerpener Strasse 62, 50937 Cologne, Germany
5Physiology Department, Faculty of Medicine (Kasr El-Aini), Cairo University, El-Maniel, Cairo 11451, Egypt

Received 7 July 2015; Revised 16 November 2015; Accepted 14 December 2015

Academic Editor: Toru Hosoda

Copyright © 2016 Jan Trieschmann 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

Transplantation of stem cell-derived cardiomyocytes is one of the most promising therapeutic approaches after myocardial infarction, as loss of cardiomyocytes is virtually irreversible by endogenous repair mechanisms. In myocardial scars, transplanted cardiomyocytes will be in immediate contact with cardiac fibroblasts. While it is well documented how the electrophysiology of neonatal cardiomyocytes is modulated by cardiac fibroblasts of the same developmental stage, it is unknown how adult cardiac fibroblasts (aCFs) affect the function of embryonic stem cell-derived cardiomyocytes (ESC-CMs). To investigate the effects of aCFs on ESC-CM electrophysiology, we performed extra- and intracellular recordings of murine aCF-ESC-CM cocultures. We observed that spontaneous beating behaviour was highly irregular in aCF-ESC-CM cocultures compared to cocultures with mesenchymal stem cells (coefficient of variation of the interspike interval: % versus %, ) and that action potential amplitude and maximal upstroke velocity () were reduced (amplitude:  mV versus  mV, :  V/s versus  V/s), while action potential duration (APD) was prolonged (APD50:  ms versus  ms, ; APD90:  ms versus  ms, ) compared to controls. Similar changes could be induced by aCF-conditioned medium. We conclude that the presence of aCFs changes automaticity and induces potentially proarrhythmic changes of ESC-CM electrophysiology.