Currently, there are no treatments that ameliorate cardiac cell death, the underlying basis of cardiovascular disease. An unexplored cell type in cardiac regeneration is cardiac Purkinje cells; specialized cells from the cardiac conduction system (CCS) responsible for propagating electrical signals. Purkinje cells have tremendous potential as a regenerative treatment because they may intrinsically integrate with the CCS of a recipient myocardium, resulting in more efficient electrical conduction in diseased hearts. This study is the first to demonstrate an effective protocol for the direct reprogramming of human cardiomyocytes into cardiac Purkinje-like cells using small molecules. The cells generated were genetically and functionally similar to native cardiac Purkinje cells, where expression of key cardiac Purkinje genes such as and the conduction of electrical signals with increased velocity was observed. This study may help to advance the quest to finding an optimized cell therapy for heart regeneration.
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http://dx.doi.org/10.1016/j.isci.2022.105402 | DOI Listing |
Nat Cardiovasc Res
January 2025
Institute of Developmental and Regenerative Medicine, University of Oxford, Oxford, UK.
Arrhythmias are a hallmark of myocardial infarction (MI) and increase patient mortality. How insult to the cardiac conduction system causes arrhythmias following MI is poorly understood. Here, we demonstrate conduction system restoration during neonatal mouse heart regeneration versus pathological remodeling at non-regenerative stages.
View Article and Find Full Text PDFHeart Rhythm
December 2024
Christian-Albrechts-University, Medical Faculty, Christian-Albrechts-Platz 4, 24118 Kiel, Germany; University of Applied Science, Life Sciences, An der Karlstadt 8, 27568 Bremerhaven, Germany. Electronic address:
Left bundle branch block (LBBB) causes immediate electrical and mechanical dys-synchrony of the left ventricle (LV) and gradual structural damages in the Purkinje cells and myocardium. Mechanical dys-synchrony reduces the LV ejection fraction (EF) instantly, but only to ≈55% in an otherwise normal heart. Because of the heart's in-built functional redundancy, a patient with LBBB does not always notice the heart's reduced efficiency straight away.
View Article and Find Full Text PDFAm J Case Rep
December 2024
Department of Cardiac Pacing and Electrophysiology, Fortis Escorts Heart Institute (FEHI), New Delhi, India.
BACKGROUND Second-degree atrioventricular (AV) block is a frequently encountered conduction abnormality on surface electrocardiogram (ECG). However, it does not always imply a block at the AV nodal level. In rare cases, this block can occur below the bundle of His, within the infra-Hisian region of the His-Purkinje system.
View Article and Find Full Text PDFComput Biol Med
December 2024
Research Center E. Piaggio, University of Pisa, L. Lazzarino, 1, Pisa, 56122, Italy; Information Engineering Department, University of Pisa, G. Caruso, 16, Pisa, 56122, Italy.
In this paper, we present CardioMat, a Matlab toolbox for cardiac electrophysiology simulation based on patient-specific anatomies. The strength of CardioMat is the easy and fast construction of electrophysiology cardiac digital twins from segmented anatomical images in a general-purpose software such as Matlab. CardioMat implements a quasi-automatic pipeline that guides the user toward the construction of anatomically detailed cardiac electrophysiology models.
View Article and Find Full Text PDFMed Eng Phys
December 2024
Cardiopulmonary Regenerative Engineering (CARE) Group, Centre for Biological Engineering, Wolfson School of Mechanical, Electrical and Manufacturing Engineering, Loughborough University, UK; Lower Saxony Center for Biomedical Engineering, Implant Research and Development, Hannover Medical School, Germany. Electronic address:
In the past two decades there has been rapid development in the field of computational cardiac models. These have included either (i) mechanical models that assumed simultaneous myocardial activation, or (ii) electromechanical models that assumed time-varying myocardial activation. The influence of these modelling assumptions of myocardial activation on clinically relevant metrics, like myocardial strain, commonly used for validation of cardiac models has yet to be systematically examined, leading to uncertainty over their influence on the predictions of these models.
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