The Interaction between Adult Cardiac Fibroblasts and Embryonic Stem Cell-Derived Cardiomyocytes Leads to Proarrhythmic Changes in In Vitro Cocultures
Transplantation of stem cell-derived cardiomyocytes is one of the most promising therapeutic approaches after myocardial infarction, as loss of cardiomyocytes is virtually irreversible by endogenous repair mechanisms. In myocardial scars, transplanted cardiomyocytes will be in immediate contact with...
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| Format: | Article |
| Language: | English |
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Wiley
2016-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2016/2936126 |
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| author | Jan Trieschmann Daniel Bettin Moritz Haustein Annette Köster Marek Molcanyi Marcel Halbach Mira Hanna Mariam Fouad Konrad Brockmeier Jürgen Hescheler Kurt Pfannkuche Tobias Hannes |
| author_facet | Jan Trieschmann Daniel Bettin Moritz Haustein Annette Köster Marek Molcanyi Marcel Halbach Mira Hanna Mariam Fouad Konrad Brockmeier Jürgen Hescheler Kurt Pfannkuche Tobias Hannes |
| author_sort | Jan Trieschmann |
| collection | DOAJ |
| description | Transplantation of stem cell-derived cardiomyocytes is one of the most promising therapeutic approaches after myocardial infarction, as loss of cardiomyocytes is virtually irreversible by endogenous repair mechanisms. In myocardial scars, transplanted cardiomyocytes will be in immediate contact with cardiac fibroblasts. While it is well documented how the electrophysiology of neonatal cardiomyocytes is modulated by cardiac fibroblasts of the same developmental stage, it is unknown how adult cardiac fibroblasts (aCFs) affect the function of embryonic stem cell-derived cardiomyocytes (ESC-CMs). To investigate the effects of aCFs on ESC-CM electrophysiology, we performed extra- and intracellular recordings of murine aCF-ESC-CM cocultures. We observed that spontaneous beating behaviour was highly irregular in aCF-ESC-CM cocultures compared to cocultures with mesenchymal stem cells (coefficient of variation of the interspike interval: 40.5±15.2% versus 9.3±2.0%, p=0.008) and that action potential amplitude and maximal upstroke velocity (Vmax) were reduced (amplitude: 52.3±1.7 mV versus 65.1±1.5 mV, Vmax: 7.0±1.0 V/s versus 36.5±5.3 V/s), while action potential duration (APD) was prolonged (APD50: 25.6±1.0 ms versus 16.8±1.9 ms, p<0.001; APD90: 52.2±1.5 ms versus 43.3±3.3 ms, p<0.01) compared to controls. Similar changes could be induced by aCF-conditioned medium. We conclude that the presence of aCFs changes automaticity and induces potentially proarrhythmic changes of ESC-CM electrophysiology. |
| format | Article |
| id | doaj-art-a80f8f4b38bb4e2fb6c8f34a6f04c64a |
| institution | Kabale University |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-a80f8f4b38bb4e2fb6c8f34a6f04c64a2025-08-20T03:38:53ZengWileyStem Cells International1687-966X1687-96782016-01-01201610.1155/2016/29361262936126The Interaction between Adult Cardiac Fibroblasts and Embryonic Stem Cell-Derived Cardiomyocytes Leads to Proarrhythmic Changes in In Vitro CoculturesJan Trieschmann0Daniel Bettin1Moritz Haustein2Annette Köster3Marek Molcanyi4Marcel Halbach5Mira Hanna6Mariam Fouad7Konrad Brockmeier8Jürgen Hescheler9Kurt Pfannkuche10Tobias Hannes11Department of Paediatric Cardiology, Heart Centre Cologne, University Hospital of Cologne, Kerpener Strasse 62, 50937 Cologne, GermanyDepartment of Paediatrics, University Hospital of Cologne, Kerpener Strasse 62, 50937 Cologne, GermanyDepartment of Paediatric Cardiology, Heart Centre Cologne, University Hospital of Cologne, Kerpener Strasse 62, 50937 Cologne, GermanyInstitute for Neurophysiology, University of Cologne, Robert-Koch-Strasse 39, 50931 Cologne, GermanyInstitute for Neurophysiology, University of Cologne, Robert-Koch-Strasse 39, 50931 Cologne, GermanyDepartment of Internal Medicine III, Heart Centre Cologne, University of Cologne, Kerpener Strasse 62, 50937 Cologne, GermanyInstitute for Neurophysiology, University of Cologne, Robert-Koch-Strasse 39, 50931 Cologne, GermanyInstitute for Neurophysiology, University of Cologne, Robert-Koch-Strasse 39, 50931 Cologne, GermanyDepartment of Paediatric Cardiology, Heart Centre Cologne, University Hospital of Cologne, Kerpener Strasse 62, 50937 Cologne, GermanyInstitute for Neurophysiology, University of Cologne, Robert-Koch-Strasse 39, 50931 Cologne, GermanyInstitute for Neurophysiology, University of Cologne, Robert-Koch-Strasse 39, 50931 Cologne, GermanyDepartment of Paediatric Cardiology, Heart Centre Cologne, University Hospital of Cologne, Kerpener Strasse 62, 50937 Cologne, GermanyTransplantation of stem cell-derived cardiomyocytes is one of the most promising therapeutic approaches after myocardial infarction, as loss of cardiomyocytes is virtually irreversible by endogenous repair mechanisms. In myocardial scars, transplanted cardiomyocytes will be in immediate contact with cardiac fibroblasts. While it is well documented how the electrophysiology of neonatal cardiomyocytes is modulated by cardiac fibroblasts of the same developmental stage, it is unknown how adult cardiac fibroblasts (aCFs) affect the function of embryonic stem cell-derived cardiomyocytes (ESC-CMs). To investigate the effects of aCFs on ESC-CM electrophysiology, we performed extra- and intracellular recordings of murine aCF-ESC-CM cocultures. We observed that spontaneous beating behaviour was highly irregular in aCF-ESC-CM cocultures compared to cocultures with mesenchymal stem cells (coefficient of variation of the interspike interval: 40.5±15.2% versus 9.3±2.0%, p=0.008) and that action potential amplitude and maximal upstroke velocity (Vmax) were reduced (amplitude: 52.3±1.7 mV versus 65.1±1.5 mV, Vmax: 7.0±1.0 V/s versus 36.5±5.3 V/s), while action potential duration (APD) was prolonged (APD50: 25.6±1.0 ms versus 16.8±1.9 ms, p<0.001; APD90: 52.2±1.5 ms versus 43.3±3.3 ms, p<0.01) compared to controls. Similar changes could be induced by aCF-conditioned medium. We conclude that the presence of aCFs changes automaticity and induces potentially proarrhythmic changes of ESC-CM electrophysiology.http://dx.doi.org/10.1155/2016/2936126 |
| spellingShingle | Jan Trieschmann Daniel Bettin Moritz Haustein Annette Köster Marek Molcanyi Marcel Halbach Mira Hanna Mariam Fouad Konrad Brockmeier Jürgen Hescheler Kurt Pfannkuche Tobias Hannes The Interaction between Adult Cardiac Fibroblasts and Embryonic Stem Cell-Derived Cardiomyocytes Leads to Proarrhythmic Changes in In Vitro Cocultures Stem Cells International |
| title | The Interaction between Adult Cardiac Fibroblasts and Embryonic Stem Cell-Derived Cardiomyocytes Leads to Proarrhythmic Changes in In Vitro Cocultures |
| title_full | The Interaction between Adult Cardiac Fibroblasts and Embryonic Stem Cell-Derived Cardiomyocytes Leads to Proarrhythmic Changes in In Vitro Cocultures |
| title_fullStr | The Interaction between Adult Cardiac Fibroblasts and Embryonic Stem Cell-Derived Cardiomyocytes Leads to Proarrhythmic Changes in In Vitro Cocultures |
| title_full_unstemmed | The Interaction between Adult Cardiac Fibroblasts and Embryonic Stem Cell-Derived Cardiomyocytes Leads to Proarrhythmic Changes in In Vitro Cocultures |
| title_short | The Interaction between Adult Cardiac Fibroblasts and Embryonic Stem Cell-Derived Cardiomyocytes Leads to Proarrhythmic Changes in In Vitro Cocultures |
| title_sort | interaction between adult cardiac fibroblasts and embryonic stem cell derived cardiomyocytes leads to proarrhythmic changes in in vitro cocultures |
| url | http://dx.doi.org/10.1155/2016/2936126 |
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