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 Cardiology2026
Optogenetic tachypacing facilitates burst-induced arrhythmia in stem cell-derived human atrial engineered heart tissue.
Karl-Felix Müller, Bangfen Pan, Julius Ridder, Jessica Schrapers, Julius Hansen, Tandy M Meier, Carl Schulz, Tim Stüdemann, Marta Lemme, Julia Krause and 13 more
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23 authors.
Karl-Felix MüllerDepartment of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.ORCID 0009-0000-5114-7983 Bangfen PanDepartment of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.ORCID 0009-0006-4929-2472 Julius RidderDZHK (German Center for Cardiovascular Research), Partner Site Hamburg/Kiel/Lübeck, 20246 Hamburg, Germany.ORCID 0009-0005-7061-8441 Jessica SchrapersDepartment of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.ORCID 0009-0008-1117-140X Tandy M MeierDepartment of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.ORCID 0009-0003-6990-9132 Carl SchulzDepartment of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.ORCID 0000-0003-0894-368X Tim StüdemannDepartment of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.ORCID 0000-0003-1987-1589 Marta LemmeDepartment of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.
Julia KrauseDZHK (German Center for Cardiovascular Research), Partner Site Hamburg/Kiel/Lübeck, 20246 Hamburg, Germany.ORCID 0000-0002-2258-038X Marc N HirtDepartment of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.ORCID 0000-0003-4728-965X Aaltje Maria Stella StoterDepartment of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.ORCID 0009-0006-9291-0686 Michael SpohnBioinformatics Core Facility, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.ORCID 0000-0001-9160-4157 Florian WeinbergerDepartment of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.ORCID 0000-0002-1961-0517 Larissa FabritzDZHK (German Center for Cardiovascular Research), Partner Site Hamburg/Kiel/Lübeck, 20246 Hamburg, Germany.ORCID 0000-0002-9241-1733 Xiaodong DuanDepartment of Neurophysiology, Institute of Physiology, University of Würzburg, Würzburg, Germany.ORCID 0000-0001-9536-5288 Shiqiang GaoDepartment of Neurophysiology, Institute of Physiology, University of Würzburg, Würzburg, Germany.ORCID 0000-0001-6190-9443 Christine E GeeDepartment of Synaptic Neuroscience, Center for Molecular Neurobiology (ZMNH), University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany.ORCID 0000-0003-0345-3665 Arne HansenDepartment of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.
Thomas EschenhagenDepartment of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.ORCID 0000-0003-1750-1170 Torsten ChristDepartment of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.ORCID 0000-0002-8935-5304 Justus StenzigDepartment of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.ORCID 0000-0003-3932-8372 Funding
DFG STE2596/4-1/456060636DFG STE2596/5-1/528380599DFG ClusterDiag 539658720DZHKJSTKFM, JSc, CS, TMMMAESTRIA EU 965286
6 · The paper itselfAbstract
aimsLarge animal models for atrial fibrillation (AF) research are ethically challenging and costly. Suitable humanized in vitro models could circumvent these problems. Here, we aimed to combine tissue engineering, human induced pluripotent stem cell-derived atrial cardiomyocytes (hiPSC-aCM), and optogenetic pacing to trigger an in vitro fibrillation-like state, which can be analysed by simple video recording. METHODS AND
resultsAtrial engineered heart tissue (aEHT) was created from hiPSC-aCM and transduced with adeno-associated virus vectors to express the channelrhodopsins CheRiff2.0, Chronos, or PsCatCh2.0f, respectively. We developed novel optogenetic hardware, based on microcontroller programmable light-emitting diodes. The interplay between aEHTs and hardware was optimized, and different pacing patterns were evaluated. Electrical burst pacing was evaluated for arrhythmia induction. Tissue constructs were analysed with regard to action potential, gene and protein expression, and structure. We found our optimized CheRiff2.0 best suitable for optogenetic pacing of aEHT at up to 5 Hz. Atrial EHT could be faithfully tachypaced at 4 Hz for 2.5 weeks. After 5 weeks, electrical burst pacing (20 Hz, 0.5 s) successfully induced self-sustained episodes of a state of fast beating, lower force, and incomplete relaxation. The propensity of these burst-evoked episodes of fibrillation was 3.2-fold higher in long-term paced aEHT than in non-paced controls. Action potential shape and gene expression recapitulated typical features of AF in the tachypaced aEHTs.
conclusionWe successfully created a first-of-its-kind in vitro model of AF, recapitulating the self-sustainability of atrial arrhythmia ('AF begets AF'). Fibrillation-like episodes can be verified by visual inspection, rendering analysis possible without an electrophysiological setup.
Indexed as
Atrial FibrillationCardiac Pacing, ArtificialHeart AtriaInduced Pluripotent Stem CellsMyocytes, CardiacOptogeneticsTissue EngineeringAction PotentialsCells, CulturedHumansAtrial fibrillationiPS cellsOptogeneticsTissue engineering
Identifiers
PMID42611532
PMCPMC13484016
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