ArticleEuropace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology2012
Genetic engineering of somatic cells to study and improve cardiac function.
Article in 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, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 16 citations in OpenAlex.
- Computational design of custom therapeutic cells to correct failing human cardiomyocytes.Frontiers in systems biology · 2023Article
- Engineered bacterial voltage-gated sodium channel platform for cardiac gene therapy.Nature communications · 2022Article
- Emerging roles of circRNAs in the pathological process of myocardial infarction.Molecular therapy. Nucleic acids · 2021Review
- Integration of Engineered "Spark-Cell" Spheroids for Optical Pacing of Cardiac Tissue.Frontiers in bioengineering and biotechnology · 2021Article
- Ion channel engineering for modulation and de novo generation of electrical excitability.Current opinion in biotechnology · 2019Review
- Generation and customization of biosynthetic excitable tissues for electrophysiological studies and cell-based therapies.Nature protocols · 2018Article
- Modeling an Excitable Biosynthetic Tissue with Inherent Variability for Paired Computational-Experimental Studies.PLoS computational biology · 2017Article
- Engineering prokaryotic channels for control of mammalian tissue excitability.Nature communications · 2016Article
- Article
- Optical mapping of optogenetically shaped cardiac action potentials.Scientific reports · 2014Article
- Robust T-tubulation and maturation of cardiomyocytes using tissue-engineered epicardial mimetics.Biomaterials · 2014Article
- Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
aimsTo demonstrate the utility of genetically engineered excitable cells for studies of basic electrophysiology and cardiac cell therapy. METHODS AND
results'Zig-zag' networks of neonatal rat ventricular myocytes (NRVMs) were micropatterned onto thin elastomeric films to mimic the slow action potential (AP) conduction found in fibrotic myocardium. Addition of genetically engineered excitable human embryonic kidney cells (HEK-293 cells) ('Ex-293' cells stably expressing Kir2.1, Na(v)1.5, and Cx43 channels) increased both cardiac conduction velocity by 370% and twitch force amplitude by 64%. Furthermore, we stably expressed mutant Na(v)1.5 [A1924T (fast sodium channel mutant (substitution of alanine by threonine at amino acid 1924)] channels with hyperpolarized steady-state activation and showed that, despite a 71.6% reduction in peak I(Na), these cells propagated APs at the same velocity as the wild-type Na(v)1.5-expressing Ex-293 cells. Stable expression of Ca(v)3.3 (T-type voltage-gated calcium) channels in Ex-293 cells (to generate an 'ExCa-293' line) significantly increased their AP duration and reduced repolarization gradients in cocultures of these cells and NRVMs. Additional expression of an optogenetic construct [ChIEF (light-gated Channelrhodopsin mutant)]enabled light-based control of AP firing in ExCa-293 cells.
conclusionWe show that, despite being non-contractile, genetically engineered excitable cells can significantly improve both electrical and mechanical function of engineered cardiac tissues in vitro. We further demonstrate the utility of engineered cells for tissue-level studies of basic electrophysiology and cardiac channelopathies. In the future, this novel platform could be utilized in the high-throughput design of new genetically encoded indicators of cell electrical function, validation, and improvement of computer models of AP conduction, and development of novel engineered somatic cell therapies for the treatment of cardiac infarction and arrhythmias.
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