Key result
MI cell therapy simulations show homogeneous populations minimize spontaneous beating and healthy Purkinje coupling prevents arrhythmias.
Why the study?
Although cell therapy for myocardial infarction offers promise, electrophysiological heterogeneity raises pro-arrhythmic safety concerns whose underlying complex spatio-temporal dynamics cannot be investigated experimentally.
Does simulated cell therapy induce arrhythmias in human-based models of acute versus chronic myocardial infarction?
Does simulated cell therapy induce arrhythmias in human-based models of acute versus chronic myocardial infarction?
In silico modeling suggests that homogeneous cell populations and healthy Purkinje-myocardium coupling are critical to minimizing the pro-arrhythmic risks of cell therapy in myocardial infarction.
Simulations suggest homogeneous cells and intact coupling may minimize MI cell therapy arrhythmias; hypothesis-generating, requires human validation before practice consideration.
Human-based modelling and simulation offer an ideal testbed for novel medical therapies to guide experimental and clinical studies. Myocardial infarction (MI) is a common cause of heart failure and mortality, for which novel therapies are urgently needed. Although cell therapy offers promise, electrophysiological heterogeneity raises pro-arrhythmic safety concerns, where underlying complex spatio-temporal dynamics cannot be investigated experimentally. After demonstrating credibility of the modelling and simulation framework, we investigate cell therapy in acute versus chronic MI, and the role of cell heterogeneity, scar size and the Purkinje system. Simulations agreed with experimental and clinical recordings from ionic to ECG dynamics in acute and chronic infarction. Following cell delivery, spontaneous beats were facilitated by heterogeneity in cell populations, chronic MI due to tissue depolarisation, and slow sinus rhythm. Subsequent re-entrant arrhythmias occurred, in some instances with Purkinje involvement, and their susceptibility was enhanced by impaired Purkinje-myocardium coupling, large scars, and acute infarction. We conclude that homogeneity in injected cell populations minimises their spontaneous beating, which is enhanced by chronic MI, whereas a healthy Purkinje-myocardium coupling is key to prevent subsequent re-entrant arrhythmias, particularly for large scars.
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Riebel et al. (2023) studied Myocardial infarction. Cell therapy vs. Acute versus chronic MI was evaluated on Spontaneous beats and re-entrant arrhythmias. Cell therapy simulations in myocardial infarction showed that homogeneous cell populations minimize spontaneous beating, while healthy Purkinje-myocardium coupling prevents re-entrant arrhythmias.
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