Implantation of Sinoatrial Node Cells into Canine Right Ventricle: Biological Pacing Appears Limited by the Substrate

Zhang, Hao; Lau, David H.; Shlapakova, Iryna N.; Zhao, Xin; Danilo, Peter; Robinson, Richard B.; Cohen, Ira S.; Qu, Dan; Zhao, Xu; Rosen, Michael R.

doi:10.3727/096368911x565038b

Cited by 15 publications

(10 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Proof of concept has been provided using a variety of approaches to increased inward current or decreased repolarising current as a basis for propagation of a pacemaker potential [8]. In this arena of research, both embryonic stem cells and human mesenchymal stem cells have been the main area of focus, although other cell sources (skeletal myoblasts; fibroblasts; cardiac stem cells) have been utilised.…”

Section: Cell-based Therapiesmentioning

confidence: 99%

See 1 more Smart Citation

Biological therapies targeting arrhythmias: are cells and genes the answer?

Falconer

Papageorgiou

Androulakis³

et al. 2017

Expert Opinion on Biological Therapy

View full text Add to dashboard Cite

Arrhythmias can cause symptoms ranging from simple dizziness to life-threatening circulatory collapse. Current management includes medical therapy and procedures such as catheter ablation or device implantation. However, these strategies still pose a risk of serious side effects, and some patients remain symptomatic. Advancement in our understanding of how arrhythmias develop on the cellular level has made more targeted approaches possible. In addition, contemporary studies have found that several genes are involved in the pathogenesis of arrhythmias. Areas covered: In the present review, the authors explore the cellular and genetic mechanisms leading to arrhythmias as well as the progress that has been made in using both gene and cell therapy to treat tachy- and bradyarrhythmias. They also consider why gene and cell therapy has resulted into a few clinical trials with promising results, however still not applicable in routine clinical practice. Expert opinion: The question currently is whether such biological therapies could replace current established approaches. The contemporary evidence suggests that despite recent advances in this field, it will need more work in experimental models before this is applied into clinical practice. Gene and cell studies targeting conduction and repolarization are promising, but still not ready for use in the clinical setting.

show abstract

Section: Cell-based Therapiesmentioning

confidence: 99%

“…Ischaemia converts conducting tissue into an electrically inactive scar, forcing the wave front into a region of slowconducting tissue, creating an environment suitable for reentry [2,7]. Fibrosis occurs in pacemaker cells as part of the aging process, resulting in bradycardia [8].…”

Section: Introductionmentioning

confidence: 99%

Biological therapies targeting arrhythmias: are cells and genes the answer?

Falconer

Papageorgiou

Androulakis³

et al. 2017

Expert Opinion on Biological Therapy

View full text Add to dashboard Cite

show abstract

“…65–67 In yet another proof-of-principle experiments, autologous SAN pacemaker cells were harvested, then transplanted back into the same animal in a dog model of sinus disorders for rhythm regeneration. 68 …”

Section: Electronic Pacemakers For Heart Rhythm Disordersmentioning

confidence: 99%

Gene- and cell-based bio-artificial pacemaker: what basic and translational lessons have we learned?

2012

Gene Ther

View full text Add to dashboard Cite

Normal rhythms originate in the sino-atrial node, a specialized cardiac tissue consisting of only a few thousands of nodal pacemaker cells. Malfunction of pacemaker cells due to diseases or aging leads to rhythm generation disorders (for example, bradycardias and sick-sinus syndrome (SSS)), which often necessitate the implantation of electronic pacemakers. Although effective, electronic devices are associated with such shortcomings as limited battery life, permanent implantation of leads, lead dislodging, the lack of autonomic responses and so on. Here, various gene-and cell-based approaches, with a particular emphasis placed on the use of pluripotent stem cells and the hyperpolarization-activated cyclic nucleotide-gated-encoded pacemaker gene family, that have been pursued in the past decade to reconstruct bio-artificial pacemakers as alternatives will be discussed in relation to the basic biological insights and translational regenerative potential. Gene Therapy (2012) 19, 588-595; doi:10.1038/gt.2012.33Keywords: human embryonic stem cells; pluripotent; bio-artificial; pacemaker; cardiac differentiation; electrophysiologyThe heart beats with a regular rhythm to pump blood throughout the body. These mechanical actions require the highly coordinated efforts of different types of cardiomyocytes (CMs) such as atrial, ventricular and pacemaker cells. Chamber-specific CM types differ substantially in their electrical properties, which in turn govern cardiac excitability. Normal heart (sinus) rhythms originate in the sino-atrial node (SAN), a specialized cardiac tissue consisting of only a few thousands nodal or so-called pacemaker cells. 1,2 The SAN spontaneously and rhythmically generates action potentials (APs) by the process of pacemaking. These rhythmic APs propagate through the atria to the atrioventricular node, and after a slow pause, subsequently to the ventricles via a unique conduction system for coordinated chamber contractions and therefore blood pumping. As such, the SAN is responsible for initiating and controlling the heart rate. CLASSICAL VIEW OF CARDIAC PACEMAKING: SAN IS A COMPLEX STRUCTURE THAT FUNCTIONS WITH A COMPLEX MECHANISMStructurally, the native SAN is a complex, three-dimensional tissue containing a heterogeneous population of pacemaker cells that display a range of phenotypic properties and anatomic boundary effects. 1,3 For instance, there are gradual gradient changes in the AP profile, 4,5 ionic current densities and gap-junction expression from central (dominant or the leading pacemaker site) to peripheral (subsidiary) SAN cells. 1 These differences and anatomic arrangements (for example, interdigitation) have been thought to ensure that the leading center cells are protected from any over-hyperpolarizing effects from the surrounding mass of atrial CMs and that the depolarization wave front is propagated in the proper directions. In addition to pacemaker cells, the SAN also contains atrial CMs, fibroblasts and adipocytes. The collagen content of the SAN region is relatively high. 6 Dur...

show abstract

“…Human Mesenchymal Stem Cells (hMSC) are multipotent stromal cells, which can be isolated from various sources, such as the umbilical cord, amniotic fluid, dental pulp, adipose tissue, etc. Brown adipose tissue has also been found to be a good source of mesenchymal stem cells [22]. They are a suitable candidate, being relatively immunopriveleged and expressing two cardiac gap junction proteins, connexins 40 and 43 [28].…”

Section: Cell-based Approachmentioning

confidence: 99%

“…It was shown that it is possible to use CD 166 expression to select SAN precursor cells [20]. However, attempts to autologously graft the SAN or inject the myocytes failed to provide sustained biological pacemaker activity [21,22]. Instead, human Embryonic Stem Cells (hESC) derived myocytes were studied as the source of cells for creating biological pacemakers.…”

Section: Cell-based Approachmentioning

confidence: 99%

Biological Pacemakers – A Review

Gunasekaran

Selvaraj

2018

ijcp

View full text Add to dashboard Cite

Slow heart rates, due to sinus node disease or atrioventricular conduction block, are a significant problem for many patients. Currently, these patients are treated with electronic pacemakers, which provide effective therapy, but are also associated with many problems. Use of biological pacemakers is an attractive solution to these problems. Approaches for the creation of such pacemakers include either the injection of cells that have pacemaker activity (cell-based approach) or modification of cells in the heart to induce pacemaker activity by delivering genes (gene-based approach). This article reviews the progress in the development of biological pacemakers.

show abstract

Implantation of Sinoatrial Node Cells into Canine Right Ventricle: Biological Pacing Appears Limited by the Substrate

Cited by 15 publications

References 25 publications

Biological therapies targeting arrhythmias: are cells and genes the answer?

Biological therapies targeting arrhythmias: are cells and genes the answer?

Gene- and cell-based bio-artificial pacemaker: what basic and translational lessons have we learned?

Biological Pacemakers – A Review

Contact Info

Product

Resources

About