Reprogramming the conduction system: Onward toward a biological pacemaker

Meyers, Jason D.; Jay, Patrick Y.

doi:10.1016/j.tcm.2015.03.015

Cited by 13 publications

(9 citation statements)

References 44 publications

(43 reference statements)

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“…Despite many useful properties of AAV, including prolonged in vivo expression and minimal immune response, significant limitations include difficulty producing sufficiently high titers, its restricted packaging capacity, and slow kinetics of transgene expression, which limits many applications. On this basis, several groups are adapting adenovirus (Ad) for cardiovascular gene therapy applications 40 41 42 43 . In this regard, two key facets of the Ad vector currently limiting its fullest utility are its dependence on the coxsackievirus and adenovirus receptor (CAR) for infectivity, and host anti-vector immune response.…”

Section: Discussionmentioning

confidence: 99%

Human Organotypic Cultured Cardiac Slices: New Platform For High Throughput Preclinical Human Trials

Kang

Qiao

et al. 2016

Sci Rep

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Translation of novel therapies from bench to bedside is hampered by profound disparities between animal and human genetics and physiology. The ability to test for efficacy and cardiotoxicity in a clinically relevant human model system would enable more rapid therapy development. We have developed a preclinical platform for validation of new therapies in human heart tissue using organotypic slices isolated from donor and end-stage failing hearts. A major advantage of the slices when compared with human iPS-derived cardiomyocytes is that native tissue architecture and extracellular matrix are preserved, thereby allowing investigation of multi-cellular physiology in normal or diseased myocardium. To validate this model, we used optical mapping of transmembrane potential and calcium transients. We found that normal human electrophysiology is preserved in slice preparations when compared with intact hearts, including slices obtained from the region of the sinus node. Physiology is maintained in slices during culture, enabling testing the acute and chronic effects of pharmacological, gene, cell, optogenetic, device, and other therapies. This methodology offers a powerful high-throughput platform for assessing the physiological response of the human heart to disease and novel putative therapies.

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Section: Discussionmentioning

confidence: 99%

Human Organotypic Cultured Cardiac Slices: New Platform For High Throughput Preclinical Human Trials

Kang

Qiao

et al. 2016

Sci Rep

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“…They are called biological pacemakers. There are lot of studies on these futuristic pacemakers, including the involvement of T-box transcription factor-18 (TBX-18) gene, TBX-3 gene, and Hyperpolarisation-activated Cyclic Nucleotide (HCN) gated channels (as seen in Figure 12) [6,34,35,36].…”

Section: Discussionmentioning

confidence: 99%

Leadless Cardiac Pacemaker as a Novel Intervention Modality for Atrioventricular Conduction Disturbance in Hypertrophic Cardiomyopathy

Sutanto

2017

J.ATAMIS

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Atrioventricular conduction disturbance is a common complication of cardiovascular diseases, such as hypertrophic cardiomyopathy. Moreover, the most common form of atrioventricular conduction disturbance is atrioventricular block. Until recently, cardiac pacing was considered to be the most reliable long-time management of atrioventricular block. However, cardiac pacemakers have several limitations and complications. When the first generation of leadless pacemakers was invented in the 1980s, it was multi-component. Nowadays, self-contained or single component leadless pacemakers have been developed and have become popular amongst cardiac electrophysiologists. In particular, in 2013, St. Jude Medical developed a novel design for a cardiac pacemaker called the NanostimTM Leadless Pacemaker. In 2015, Medtronic released a smaller leadless pacemaker called the MicraTM Transcatheter Pacing System.1,2 Although NanostimTM and MicraTM represent state of the art technology; a few studies have documented some of their limitations.3-6 More research is needed to confirm and solve these problems

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“…These promising studies have been recently reviewed elsewhere and will not be described in this article. [6–9]…”

Section: Cardiac Conduction System Disease and The Need For Biologicamentioning

confidence: 99%

“…Several of these hurdles, including the development of improved delivery methods of genes and cells to target areas, the possibility of pro-arrhythmic effects of biological pacemakers, and the potential for off-target or oncogenic effects of stem cell and transcription-factor based therapies have been recently reviewed and are not detailed here [6, 7] Moreover, there may be genetic factors that predispose patients – particularly younger ones -- to PC dysfunction. In such cases, reprogramming with the patient’s own cells could result in dysfunctional PCs and suboptimal results.…”

Section: Clinical Translationmentioning

confidence: 99%

New Approaches to Biological Pacemakers: Links to Sinoatrial Node Development

Vedantham

2015

Trends in Molecular Medicine

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Irreversible degeneration of the cardiac conduction system is a common disease that can cause activity intolerance, fainting, and death. While electronic pacemakers provide effective treatment, alternative approaches are needed when long-term indwelling hardware is undesirable. Biological pacemakers are composed of electrically active cells that functionally integrate with the heart. Recent findings on cardiac pacemaker cells (PCs) within the sinoatrial node (SAN), along with developments in stem cell technology, have opened a new era in biological pacing. Recent experiments that have derived PC-like cells from non-PCs have brought the field closer than ever before to biological pacemakers that can faithfully recapitulate SAN activity. This review discusses these approaches in the context of SAN biology and addresses the potential for clinical translation.

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Reprogramming the conduction system: Onward toward a biological pacemaker

Cited by 13 publications

References 44 publications

Human Organotypic Cultured Cardiac Slices: New Platform For High Throughput Preclinical Human Trials

Human Organotypic Cultured Cardiac Slices: New Platform For High Throughput Preclinical Human Trials

Leadless Cardiac Pacemaker as a Novel Intervention Modality for Atrioventricular Conduction Disturbance in Hypertrophic Cardiomyopathy

New Approaches to Biological Pacemakers: Links to Sinoatrial Node Development

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