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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 10:2608 (2021)
Publ. Version/Full Text DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords 3d Culture ; Cardiomyocytes ; Maturation ; Risk Assessment ; Stem Cell Differentiation ; Structural Remodeling ; X-rays; Pluripotent Stem-cells; Induced Heart-disease; Radiation; Maturation; Radiotherapy; Proteome
ISSN (print) / ISBN 2073-4409
e-ISSN 2073-4409
Journal Cells
Quellenangaben Volume: 10, Issue: 10, Pages: , Article Number: 2608 Supplement: ,
Publisher MDPI
Publishing Place Basel
Non-patent literature Publications
Institute(s) Institute of Radiation Medicine (IRM)
CF Metabolomics & Proteomics (CF-MPC)
Grants Helmholtz Graduate School for Hadron and Ion Research