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hESC derived cardiomyocyte biosensor to detect the different types of arrhythmogenic properties of drugs
R. Pivato, S. Klimovic, D. Kabanov, F. Sverák, M. Pesl, J. Pribyl, V. Rotrekl
Status minimální Jazyk angličtina Země Nizozemsko
Typ dokumentu časopisecké články
Grantová podpora
NU20-06-00156
MZ0
CEP - Centrální evidence projektů
- MeSH
- biosenzitivní techniky * MeSH
- kardiomyocyty MeSH
- lidé MeSH
- lidské embryonální kmenové buňky * MeSH
- srdeční arytmie chemicky indukované diagnóza MeSH
- vápník MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
In the present work, we introduce a new cell-based biosensor for detecting arrhythmias based on a novel utilization of the combination of the Atomic Force Microscope (AFM) lateral force measurement as a nanosensor with a dual 3D cardiomyocyte syncytium. Two spontaneously coupled clusters of cardiomyocytes form this. The syncytium's functional contraction behavior was assessed using video sequences analyzed with Musclemotion ImageJ/Fiji software, and immunocytochemistry evaluated phenotype composition. The application of caffeine solution induced arrhythmia as a model drug, and its spontaneous resolution was monitored by AFM lateral force recording and interpretation and calcium fluorescence imaging as a reference method describing non-synchronized contractions of cardiomyocytes. The phenotypic analysis revealed the syncytium as a functional contractile and conduction cardiac behavior model. Calcium fluorescence imaging was used to validate that AFM fully enabled to discriminate cardiac arrhythmias in this in vitro cellular model. The described novel 3D hESCs-based cellular biosensor is suitable to detect arrhythmic events on the level of cardiac contractile and conduction tissue cellular model. The resulting biosensor allows for screening of arrhythmogenic properties of tailored drugs enabling its use in precision medicine.
Citace poskytuje Crossref.org
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- $a Pivato, Roberto $u Department of Biology, Faculty of Medicine, Masaryk University, Kamenice 5, 625 00, Brno, Czech Republic; International Clinical Research Center at St. Anne's University Hospital, Pekarská 53, 65691, Brno, Czech Republic
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- $a hESC derived cardiomyocyte biosensor to detect the different types of arrhythmogenic properties of drugs / $c R. Pivato, S. Klimovic, D. Kabanov, F. Sverák, M. Pesl, J. Pribyl, V. Rotrekl
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- $a In the present work, we introduce a new cell-based biosensor for detecting arrhythmias based on a novel utilization of the combination of the Atomic Force Microscope (AFM) lateral force measurement as a nanosensor with a dual 3D cardiomyocyte syncytium. Two spontaneously coupled clusters of cardiomyocytes form this. The syncytium's functional contraction behavior was assessed using video sequences analyzed with Musclemotion ImageJ/Fiji software, and immunocytochemistry evaluated phenotype composition. The application of caffeine solution induced arrhythmia as a model drug, and its spontaneous resolution was monitored by AFM lateral force recording and interpretation and calcium fluorescence imaging as a reference method describing non-synchronized contractions of cardiomyocytes. The phenotypic analysis revealed the syncytium as a functional contractile and conduction cardiac behavior model. Calcium fluorescence imaging was used to validate that AFM fully enabled to discriminate cardiac arrhythmias in this in vitro cellular model. The described novel 3D hESCs-based cellular biosensor is suitable to detect arrhythmic events on the level of cardiac contractile and conduction tissue cellular model. The resulting biosensor allows for screening of arrhythmogenic properties of tailored drugs enabling its use in precision medicine.
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- $a Klimovic, Simon $u International Clinical Research Center at St. Anne's University Hospital, Pekarská 53, 65691, Brno, Czech Republic; Department of Biochemistry, Faculty of Science, Masaryk University, Kamenice 753/5, 625 00, Brno, Czech Republic; Central European Institute for Technology, Masaryk University, Kamenice 753/5, 625 00, Brno, Czech Republic
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- $a Kabanov, Daniil $u Department of Biochemistry, Faculty of Science, Masaryk University, Kamenice 753/5, 625 00, Brno, Czech Republic; Central European Institute for Technology, Masaryk University, Kamenice 753/5, 625 00, Brno, Czech Republic
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- $a Sverák, Filip $u Department of Biology, Faculty of Medicine, Masaryk University, Kamenice 5, 625 00, Brno, Czech Republic; International Clinical Research Center at St. Anne's University Hospital, Pekarská 53, 65691, Brno, Czech Republic
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- $a Pesl, Martin $u Department of Biology, Faculty of Medicine, Masaryk University, Kamenice 5, 625 00, Brno, Czech Republic; International Clinical Research Center at St. Anne's University Hospital, Pekarská 53, 65691, Brno, Czech Republic; First Department of Internal Medicine - Cardioangiology, Faculty of Medicine, Masaryk University and St. Anne's University Hospital, Pekarská 53, 65691, Brno, Czech Republic
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- $a Pribyl, Jan $u Central European Institute for Technology, Masaryk University, Kamenice 753/5, 625 00, Brno, Czech Republic. Electronic address: jan.pribyl@ceitec.muni.cz
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- $a Rotrekl, Vladimir $u Department of Biology, Faculty of Medicine, Masaryk University, Kamenice 5, 625 00, Brno, Czech Republic; International Clinical Research Center at St. Anne's University Hospital, Pekarská 53, 65691, Brno, Czech Republic. Electronic address: vrotrekl@med.muni.cz
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