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Article

A Human 3D Cardiomyocyte Risk Model to Study the Cardiotoxic Influence of X-rays and Other Noxae in Adults

1
Biophysics Department, GSI Helmholtzzentrum für Schwerionenforschung GmbH, 64291 Darmstadt, Germany
2
Biology Department, Technische Universität Darmstadt, 64289 Darmstadt, Germany
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Section Radiation Biology, Federal Office for Radiation Protection (BfS), 85764 Neuherberg, Germany
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Helmholtz Zentrum München-German Research Center for Environmental Health, Institute of Radiation Biology, 85764 Neuherberg, Germany
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Helmholtz Zentrum München-German Research Center for Environmental Health, Research Unit Protein Science, 80939 Munich, Germany
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Institute for Condensed Matter Physics, Technische Universität Darmstadt, 64289 Darmstadt, Germany
*
Author to whom correspondence should be addressed.
Academic Editors: Barbara Barboni, Valentina Russo and Nicola Bernabò
Cells 2021, 10(10), 2608; https://doi.org/10.3390/cells10102608
Received: 27 August 2021 / Revised: 23 September 2021 / Accepted: 26 September 2021 / Published: 30 September 2021
The heart tissue is a potential target of various noxae contributing to the onset of cardiovascular diseases. However, underlying pathophysiological mechanisms are largely unknown. Human stem cell-derived models are promising, but a major concern is cell immaturity when estimating risks for adults. In this study, 3D aggregates of human embryonic stem cell-derived cardiomyocytes were cultivated for 300 days and characterized regarding degree of maturity, structure, and cell composition. Furthermore, effects of ionizing radiation (X-rays, 0.1–2 Gy) on matured aggregates were investigated, representing one of the noxae that are challenging to assess. Video-based functional analyses were correlated to changes in the proteome after irradiation. Cardiomyocytes reached maximum maturity after 100 days in cultivation, judged by α-actinin lengths, and displayed typical multinucleation and branching. At this time, aggregates contained all major cardiac cell types, proven by the patch-clamp technique. Matured and X-ray-irradiated aggregates revealed a subtle increase in beat rates and a more arrhythmic sequence of cellular depolarisation and repolarisation compared to non-irradiated sham controls. The proteome analysis provides first insights into signaling mechanisms contributing to cardiotoxicity. Here, we propose an in vitro model suitable to screen various noxae to target adult cardiotoxicity by preserving all the benefits of a 3D tissue culture. View Full-Text
Keywords: cardiomyocytes; maturation; X-rays; stem cell differentiation; risk assessment; structural remodeling; 3D culture cardiomyocytes; maturation; X-rays; stem cell differentiation; risk assessment; structural remodeling; 3D culture
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MDPI and ACS Style

Smit, T.; Schickel, E.; Azimzadeh, O.; von Toerne, C.; Rauh, O.; Ritter, S.; Durante, M.; Schroeder, I.S. A Human 3D Cardiomyocyte Risk Model to Study the Cardiotoxic Influence of X-rays and Other Noxae in Adults. Cells 2021, 10, 2608. https://doi.org/10.3390/cells10102608

AMA Style

Smit T, Schickel E, Azimzadeh O, von Toerne C, Rauh O, Ritter S, Durante M, Schroeder IS. A Human 3D Cardiomyocyte Risk Model to Study the Cardiotoxic Influence of X-rays and Other Noxae in Adults. Cells. 2021; 10(10):2608. https://doi.org/10.3390/cells10102608

Chicago/Turabian Style

Smit, Timo, Esther Schickel, Omid Azimzadeh, Christine von Toerne, Oliver Rauh, Sylvia Ritter, Marco Durante, and Insa S. Schroeder 2021. "A Human 3D Cardiomyocyte Risk Model to Study the Cardiotoxic Influence of X-rays and Other Noxae in Adults" Cells 10, no. 10: 2608. https://doi.org/10.3390/cells10102608

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