A comprehensive, multiscale framework for evaluation of arrhythmias arising from cell therapy in the whole post-myocardial infarcted heart
| Autor: | William H. Franceschi, Patrick M. Boyle, Farhad Pashakhanloo, Joseph K. Yu, Natalia A. Trayanova, Qinwen Huang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cardiac function curve Pluripotent Stem Cells Heart block Cell- and Tissue-Based Therapy Myocardial Infarction lcsh:Medicine Article Cell therapy 03 medical and health sciences 0302 clinical medicine Medicine Computational models Animals Regeneration Myocytes Cardiac Myocardial infarction lcsh:Science Ventricular contractility Multidisciplinary business.industry Transdifferentiation lcsh:R Arrhythmias Cardiac Cell Differentiation Reentry Models Theoretical medicine.disease 030104 developmental biology Infarcted heart lcsh:Q Cardiac regeneration Rabbits business Neuroscience 030217 neurology & neurosurgery Stem Cell Transplantation |
| Zdroj: | Scientific Reports, Vol 9, Iss 1, Pp 1-16 (2019) Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-019-45684-0 |
| Popis: | Direct remuscularization approaches to cell-based heart repair seek to restore ventricular contractility following myocardial infarction (MI) by introducing new cardiomyocytes (CMs) to replace lost or injured ones. However, despite promising improvements in cardiac function, high incidences of ventricular arrhythmias have been observed in animal models of MI injected with pluripotent stem cell-derived cardiomyocytes (PSC-CMs). The mechanisms of arrhythmogenesis remain unclear. Here, we present a comprehensive framework for computational modeling of direct remuscularization approaches to cell therapy. Our multiscale 3D whole-heart modeling framework integrates realistic representations of cell delivery and transdifferentiation therapy modalities as well as representation of spatial distributions of engrafted cells, enabling simulation of clinical therapy and the prediction of emergent electrophysiological behavior and arrhythmogenensis. We employ this framework to explore how varying parameters of cell delivery and transdifferentiation could result in three mechanisms of arrhythmogenesis: focal ectopy, heart block, and reentry. |
| Databáze: | OpenAIRE |
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