Biological Modification of Arrhythmogenic Substrates by Cell-Free Therapeutics

Abstract

Ventricular arrhythmias (VAs) represent a major cause of sudden cardiac death and afflict patients with heart failure from both ischaemic and non-ischaemic origins, and inherited cardiomyopathies. Current VA management, including anti-arrhythmic medications, autonomic modulation, implantable cardioverter-defibrillator implantation, and catheter ablation, remains suboptimal. Catheter ablation may even cause significant cardiomyocyte loss. Cell-based therapies and exosome treatment have been proposed as promising strategies to lessen cardiomyocyte death, modulate immune reaction, and reduce myocardial scarring, and, therefore, are potentially beneficial in treating VAs. In this review, we summarise the current cornerstones of VA management. We also discuss recent advances and ongoing evidence regarding cell-based and exosome therapy, with special attention to VA treatment.

Keywords: Cardiosphere-derived cells; Catheter ablation; Exosomes; Extracellular Vesicles; Stem cells; Ventricular arrhythmias.

Figure 1

Summary of the effects of catheter ablation and exosome-based therapies on the ventricular arrhythmogenic substrate.

Figure 2

Effects of exosome-based therapy on arrhythmogenic cardiomyopathy. (A) Quantification of ventricular arrhythmias over twenty-four hours. (B) Incidence of ventricular tachycardia and fibrillation induced by programmed electrical stimulation. (C) Representative gross pathology (top) and Masson’s trichrome-stained micrographs. (D) Representative images from immunohistochemical staining for nuclear factor-kB and α-sarcomeric actinin (ASA) and quantification of nuclei positive for nuclear factor-kB. Reproduced with permission from (Lin et al., 2021) [59]. Copyright © 2023, Oxford University Press. Abbreviations: VAs, ventricular arrhythmias; VT, ; VF, ; Dsg2, ; WT, ; Veh, ; EV, ; DSG2; MT, ; RV, LV,

Figure 3

Effects of exosome-based therapy on ischemia cardiomyopathy. (A) Representative traces of programmed electrical stimulation in a porcine model of myocardial infarction. (B) Representative isochronal maps of areas of late activation in myocardial infarction. (C) Picrosirius red-stained sections of the infarct zone of infarcted pigs. Reproduced with permission from (Dawkins et al., 2022) [60]. Copyright © 2023, Oxford University Press. Abbreviations: CDC_EXO,.