ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2019
Engineered Cardiac Pacemaker Nodes Created by TBX18 Gene Transfer Overcome Source-Sink Mismatch.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 24 citations in OpenAlex.
- Biomechanical Isolation is Required for Maintenance of the Cardiac Pacemaker Cell Fate.Research square · 2026Article
- Mechanisms of rectified gap junctional coupling enhancing pacemaking activity of biologically engineered pacemaker cells.NPJ systems biology and applications · 2026Article
- Promoting differentiation of human-induced pluripotent stem cells into sinoatrial node-like cells through programmed regulation of AMPK signalling pathway.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2025Article
- Gene Therapy for Cardiac Arrhythmias: Mechanisms, Modalities and Therapeutic Applications.Medical sciences (Basel, Switzerland) · 2025Review
- Tissue elasticity modulates cardiac pacemaker cell automaticity.American journal of physiology. Heart and circulatory physiology · 2025Article
- Transient pacing in pigs with complete heart block via myocardial injection of mRNA coding for the T-box transcription factor 18.Nature biomedical engineering · 2024Article
- Local tissue mechanics control cardiac pacemaker cell embryonic patterning.Life science alliance · 2023Article
- Comparative Study of Transcriptome in the Hearts Isolated from Mice, Rats, and Humans.Biomolecules · 2022Article
- DNA Tension Probes Show that Cardiomyocyte Maturation Is Sensitive to the Piconewton Traction Forces Transmitted by Integrins.ACS nano · 2022Article
- Implementing Biological Pacemakers: Design Criteria for Successful.Circulation. Arrhythmia and electrophysiology · 2021Review
- Adherens junction engagement regulates functional patterning of the cardiac pacemaker cell lineage.Developmental cell · 2021Article
- Assembly of the Cardiac Pacemaking Complex: Electrogenic Principles of Sinoatrial Node Morphogenesis.Journal of cardiovascular development and disease · 2021Review
- Bioengineering the Cardiac Conduction System: Advances in Cellular, Gene, and Tissue Engineering for Heart Rhythm Regeneration.Frontiers in bioengineering and biotechnology · 2021Review
- Integration of Engineered "Spark-Cell" Spheroids for Optical Pacing of Cardiac Tissue.Frontiers in bioengineering and biotechnology · 2021Article
- Cellular Reprogramming Approaches to Engineer Cardiac Pacemakers.Current cardiology reports · 2020Review
- The Quantitative Relationship among the Number of the Pacing Cells Required, the Dimension, and the Diffusion Coefficient.BioMed research international · 2020Article
- Engineered Cardiac Pacemaker Nodes Created by TBX18 Gene Transfer Overcome Source-Sink Mismatch.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2019Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
Every heartbeat originates from a tiny tissue in the heart called the sinoatrial node (SAN). The SAN harbors only ≈10 000 cardiac pacemaker cells, initiating an electrical impulse that captures the entire heart, consisting of billions of cardiomyocytes for each cardiac contraction. How these rare cardiac pacemaker cells (the electrical source) can overcome the electrically hyperpolarizing and quiescent myocardium (the electrical sink) is incompletely understood. Due to the scarcity of native pacemaker cells, this concept of source-sink mismatch cannot be tested directly with live cardiac tissue constructs. By exploiting TBX18 induced pacemaker cells by somatic gene transfer, 3D cardiac pacemaker spheroids can be tissue-engineered. The TBX18 induced pacemakers (sphTBX18) pace autonomously and drive the contraction of neighboring myocardium in vitro. TBX18 spheroids demonstrate the need for reduced electrical coupling and physical separation from the neighboring ventricular myocytes, successfully recapitulating a key design principle of the native SAN. β-Adrenergic stimulation as well as electrical uncoupling significantly increase sphTBX18s' ability to pace-and-drive the neighboring myocardium. This model represents the first platform to test design principles of the SAN for mechanistic understanding and to better engineer biological pacemakers for therapeutic translation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.