Editorial CommentaryBiological pacemakers: Ready for the clinic?
Section snippets
Preferred biological agent
As the authors acknowledged in their review, cell-based approaches have less robust pre-clinical data and are less likely to reach the clinic due to safety concerns such as arrhythmogenicity, teratoma formation, and migration from the injection site. Gene therapy approaches by either over-expression of pacemaker channel genes or somatic reprogramming by a single transcription factor (TBX18) are undoubtedly closer to clinical translation. Ion channel-based approaches are designed to produce
Patient selection for the first-in-human trial
While the ultimate goal may be to replace the electronic pacemaker, it is important to be realistic in thinking about potential first-in-human applications. Device-related infections have been rising in the past decade not only due to an increase in device implantations, but also due to a higher incidence of bacterial infections in the US and worldwide, with significant associated morbidity and mortality [5], [6]. Patients with device-related infections generally require complete removal of all
Preferred delivery system
Although BioP have been successfully created in large animals by gene transfer, the delivery methods have been extremely invasive (open-chest or trans-arterial) approaches [9], [10], [11] limiting their potential for human translation. A minimally invasive delivery technique using right-sided catheterization has been recently optimized for the delivery of BioP, avoiding access to the arterial circulation with consequent risk of vascular complications or stroke [2], [12]. The article by Boink et
Conclusion
Ion channel-based and reprogramming-based BioP strategies have been carefully characterized in pre-clinical models of conduction disease. With appropriate attention to all the nuances, it seems likely that BioP strategies will soon make the transition from much hyped technology to actual clinical testing.
Acknowledgment
The author would like to thank Dr. Eduardo Marbán for helpful discussions.
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Cited by (12)
Gene and Cell Therapy for Cardiac Arrhythmias
2020, Clinical TherapeuticsCitation Excerpt :Electronic pacemakers are of great value for the treatment of cardiac conduction disease. Although effective, they have limitations related to lead or generator malfunction, lack of autonomic responsiveness, undesirable interactions with strong magnetic fields, and device-related infections.24–29 These limitations have motivated the quest for biological alternatives over the years with the aim to enhance cardiac automaticity to provide an adjunct or replacement to conventional treatment.
Generation of cardiac pacemaker cells by programming and differentiation
2016, Biochimica et Biophysica Acta - Molecular Cell ResearchCitation Excerpt :However, the current developmental state of biological pacemaker is at best in an early phase although first studies already realized in a small or large animal model exist. In the last time, several reviews and commentaries discuss about the gene transfer realized by viral transfection of adult hearts with Tbx18 [61–65]. This study has demonstrated that a biological pacemaker created by minimally invasive somatic reprogramming by viral delivery of Tbx18 in pigs can pace the heart after a complete heart block [57].
Recreating the Sinus Node by Somatic Reprogramming: A Dream Come True?
2015, Revista Espanola de CardiologiaLocal tissue mechanics control cardiac pacemaker cell embryonic patterning
2023, Life Science AllianceA Simulation Study on the Reentrant Waves in the Pacing Ventricular Tissues
2021, Journal of Physics: Conference SeriesAssembly of the cardiac pacemaking complex: Electrogenic principles of sinoatrial node morphogenesis
2021, Journal of Cardiovascular Development and Disease
Funding: Supported by NIH, USA/National Center for Advancing Translational Science (NCATS) UCLA CTSI Grant Number UL1TR000124, Cedars-Sinai Board of Governors Heart Stem Cell Center, USA.
The author has indicated there are no conflicts of interest.