Universität zu Köln

Trieschmann, Jan, Bettin, Daniel, Haustein, Moritz, Koester, Annette, Molcanyi, Marek, Halbach, Marcel, Hanna, Mira ORCID: 0000-0002-5052-8335, Fouad, Mariam, Brockmeier, Konrad, Hescheler, Juergen, Pfannkuche, Kurt and Hannes, Tobias ORCID: 0000-0002-8550-2282 (2016). The Interaction between Adult Cardiac Fibroblasts and Embryonic Stem Cell-Derived Cardiomyocytes Leads to Proarrhythmic Changes in In Vitro Cocultures. Stem Cells Int., 2016. LONDON: HINDAWI LTD. ISSN 1687-9678

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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: 40.5 +/- 15.2% versus 9.3 +/- 2.0%, p = 0.008) and that action potential amplitude and maximal upstroke velocity (V-max) were reduced (amplitude: 52.3 +/- 1.7 mV versus 65.1 +/- 1.5 mV, V-max: 7.0 +/- 1.0 V/s versus 36.5 +/- 5.3 V/s), while action potential duration (APD) was prolonged (APD50: 25.6 +/- 1.0 ms versus 16.8 +/- 1.9 ms, p < 0.001; APD90: 52.2 +/- 1.5 ms versus 43.3 +/- 3.3 ms, p < 0.01) 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Trieschmann, Jan UNSPECIFIED UNSPECIFIED UNSPECIFIED Bettin, Daniel UNSPECIFIED UNSPECIFIED UNSPECIFIED Haustein, Moritz UNSPECIFIED UNSPECIFIED UNSPECIFIED Koester, Annette UNSPECIFIED UNSPECIFIED UNSPECIFIED Molcanyi, Marek UNSPECIFIED UNSPECIFIED UNSPECIFIED Halbach, Marcel UNSPECIFIED UNSPECIFIED UNSPECIFIED Hanna, Mira UNSPECIFIED orcid.org/0000-0002-5052-8335 UNSPECIFIED Fouad, Mariam UNSPECIFIED UNSPECIFIED UNSPECIFIED Brockmeier, Konrad UNSPECIFIED UNSPECIFIED UNSPECIFIED Hescheler, Juergen UNSPECIFIED UNSPECIFIED UNSPECIFIED Pfannkuche, Kurt UNSPECIFIED UNSPECIFIED UNSPECIFIED Hannes, Tobias UNSPECIFIED orcid.org/0000-0002-8550-2282 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-291042
DOI:	10.1155/2016/2936126
Journal or Publication Title:	Stem Cells Int.
Volume:	2016
Date:	2016
Publisher:	HINDAWI LTD
Place of Publication:	LONDON
ISSN:	1687-9678
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ENGINEERED HEART-TISSUE; ION-CHANNEL EXPRESSION; BEAT-RATE VARIABILITY; ELECTROPHYSIOLOGICAL MATURATION; IMPULSE PROPAGATION; SINOATRIAL NODE; ENGRAFTMENT; INTEGRATION; MECHANISMS; MYOCYTES Multiple languages Cell & Tissue Engineering Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/29104