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. 2019 Jun 25;9:9238. doi: 10.1038/s41598-019-45684-0

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© The Author(s) 2019

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Hierarchy of the multi-scale whole-heart framework for simulating the electrophysiological effects of cell-based heart repair with de novo cardiomyocytes. (a) At the cell scale, two therapy modalities are represented: cell delivery (top) or transdifferentiation (bottom). (b) At the tissue scale, heterogeneous spatial distributions of remuscularized tissue (blue) among the native myocardium (red) is modeled. (c) At the organ scale, localized delivery is simulated into individualized 3D heart models of post-MI patients and the emergence of arrhythmia can be observed. Models are reconstructed from contrast-enhanced clinical MRIs and represent the distributions of grey zone (i.e., peri-infarct) and scar tissue.