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Slow conduction in mixed cultured strands of primary ventricular cells and stem cell-derived cardiomyocytes

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Kucera Jan P., Prudat Yann, Marcu Irene C., Azzarito Michela, Ullrich Nina D.,
Project Bioelectrical-biomechanical interactions in cardiac tissue and ephaptic conduction: two challenging aspects of cardiac electrophysiology
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Original article (peer-reviewed)

Journal Frontiers in Cell and Developmental Biology
Volume (Issue) 3
Page(s) 58
Title of proceedings Frontiers in Cell and Developmental Biology
DOI 10.3389/fcell.2015.00058

Open Access

URL https://www.frontiersin.org/articles/10.3389/fcell.2015.00058/full
Type of Open Access Publisher (Gold Open Access)

Abstract

Modern concepts for the treatment of myocardial diseases focus on novel cell therapeutic strategies involving stem cell-derived cardiomyocytes (SCMs). However, functional integration of SCMs requires similar electrophysiological properties as primary cardiomyocytes (PCMs) and the ability to establish intercellular connections with host myocytes in order to contribute to the electrical and mechanical activity of the heart. The aim of this project was to investigate the properties of cardiac conduction in a co-culture approach using SCMs and PCMs in cultured cell strands. Murine embryonic SCMs were pooled with fetal ventricular cells and seeded in predefined proportions on microelectrode arrays to form patterned strands of mixed cells. Conduction velocity (CV) was measured during steady state pacing. SCM excitability was estimated from action potentials measured in single cells using the patch clamp technique. Experiments were complemented with computer simulations of conduction using a detailed model of cellular architecture in mixed cell strands. CV was significantly lower in strands composed purely of SCMs (5.5 ± 1.5 cm/s, n = 11) as compared to PCMs (34.9 ± 2.9 cm/s, n = 21) at similar refractoriness (100% SCMs: 122 ± 25 ms, n = 9; 100% PCMs: 139 ± 67 ms, n = 14). In mixed strands combining both cell types, CV was higher than in pure SCMs strands, but always lower than in 100% PCM strands. Computer simulations demonstrated that both intercellular coupling and electrical excitability limit CV. These data provide evidence that in cultures of murine ventricular cardiomyocytes, SCMs cannot restore CV to control levels resulting in slow conduction, which may lead to reentry circuits and arrhythmias.
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