Characterization of human living myocardial slices culture-induced adaptations: a translational perspective
Heart failure involves complex pathophysiological processes, best studied in multicellular human cardiac tissues that reflect the native cellular composition and microenvironment. However, maintaining primary cells and tissues in culture for extended periods remains challenging. Developing robust hu...
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| Format: | Article |
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Elsevier
2025-09-01
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| Series: | Journal of Molecular and Cellular Cardiology Plus |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2772976125001849 |
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| author | Jort S.A. van der Geest Ernest Diez Benavente Willem B. van Ham Pieter A. Doevendans Linda W. van Laake Teun P. de Boer Vasco Sampaio-Pinto Joost P.G. Sluijter |
| author_facet | Jort S.A. van der Geest Ernest Diez Benavente Willem B. van Ham Pieter A. Doevendans Linda W. van Laake Teun P. de Boer Vasco Sampaio-Pinto Joost P.G. Sluijter |
| author_sort | Jort S.A. van der Geest |
| collection | DOAJ |
| description | Heart failure involves complex pathophysiological processes, best studied in multicellular human cardiac tissues that reflect the native cellular composition and microenvironment. However, maintaining primary cells and tissues in culture for extended periods remains challenging. Developing robust human cardiac models is critical for advancing preclinical research and bridging the gap to clinical applications. This study aims to characterize adaptations occurring in human living myocardial slices (LMS) during ex vivo culture.During culture, LMS demonstrated progressive enhancements in contractile function including stronger force generation, reduced diastolic tension, and faster contraction-relaxation kinetics. However, excitability and force-frequency response decreased over the same period. Cultured LMS showed enhanced calcium handling, including increased ability to follow pacing, higher amplitude, and faster, more stable calcium re-uptake. Structurally, LMS displayed no changes in sarcomeres, cell-cell connections, or mitochondria, despite gene expression changes in cytoskeletal and extracellular matrix-related pathways. Transcriptomic analysis revealed metabolic activation with upregulation of metabolism-related pathways. Interestingly, LMS exhibited increased expression of genes associated with early cardiac development after the culture period.LMS provide a powerful translational model for cardiovascular research, enabling the evaluation of novel therapies and fundamental studies. However, culture-induced adaptations must be carefully considered when interpreting results to ensure physiological and disease relevance. |
| format | Article |
| id | doaj-art-2177bb918d1b4b54995403624efb72f4 |
| institution | DOAJ |
| issn | 2772-9761 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Molecular and Cellular Cardiology Plus |
| spelling | doaj-art-2177bb918d1b4b54995403624efb72f42025-08-20T03:23:02ZengElsevierJournal of Molecular and Cellular Cardiology Plus2772-97612025-09-011310046510.1016/j.jmccpl.2025.100465Characterization of human living myocardial slices culture-induced adaptations: a translational perspectiveJort S.A. van der Geest0Ernest Diez Benavente1Willem B. van Ham2Pieter A. Doevendans3Linda W. van Laake4Teun P. de Boer5Vasco Sampaio-Pinto6Joost P.G. Sluijter7Department of Cardiology and Experimental Cardiology Laboratory, Division of Heart & Lungs, University Medical Centre Utrecht, Utrecht, the Netherlands; Regenerative Medicine Centre Utrecht, Circulatory Health Research Center, University Utrecht, University Medical Centre Utrecht, Utrecht, the NetherlandsDepartment of Cardiology and Experimental Cardiology Laboratory, Division of Heart & Lungs, University Medical Centre Utrecht, Utrecht, the NetherlandsDepartment of Medical Physiology, Division of Heart & Lungs, University Medical Centre Utrecht, Utrecht, the NetherlandsDepartment of Cardiology and Experimental Cardiology Laboratory, Division of Heart & Lungs, University Medical Centre Utrecht, Utrecht, the Netherlands; Netherlands Heart Institute (NLHI), Utrecht, the Netherlands; Central Military Hospital (CMH), Utrecht, the NetherlandsDepartment of Cardiology and Experimental Cardiology Laboratory, Division of Heart & Lungs, University Medical Centre Utrecht, Utrecht, the Netherlands; Regenerative Medicine Centre Utrecht, Circulatory Health Research Center, University Utrecht, University Medical Centre Utrecht, Utrecht, the NetherlandsDepartment of Medical Physiology, Division of Heart & Lungs, University Medical Centre Utrecht, Utrecht, the NetherlandsDepartment of Cardiology and Experimental Cardiology Laboratory, Division of Heart & Lungs, University Medical Centre Utrecht, Utrecht, the Netherlands; Regenerative Medicine Centre Utrecht, Circulatory Health Research Center, University Utrecht, University Medical Centre Utrecht, Utrecht, the Netherlands; Corresponding authors at: Department of Cardiology, Division of Heart & Lungs, University Medical Centre Utrecht, 3584 CX Utrecht, the Netherlands.Department of Cardiology and Experimental Cardiology Laboratory, Division of Heart & Lungs, University Medical Centre Utrecht, Utrecht, the Netherlands; Regenerative Medicine Centre Utrecht, Circulatory Health Research Center, University Utrecht, University Medical Centre Utrecht, Utrecht, the Netherlands; Corresponding authors at: Department of Cardiology, Division of Heart & Lungs, University Medical Centre Utrecht, 3584 CX Utrecht, the Netherlands.Heart failure involves complex pathophysiological processes, best studied in multicellular human cardiac tissues that reflect the native cellular composition and microenvironment. However, maintaining primary cells and tissues in culture for extended periods remains challenging. Developing robust human cardiac models is critical for advancing preclinical research and bridging the gap to clinical applications. This study aims to characterize adaptations occurring in human living myocardial slices (LMS) during ex vivo culture.During culture, LMS demonstrated progressive enhancements in contractile function including stronger force generation, reduced diastolic tension, and faster contraction-relaxation kinetics. However, excitability and force-frequency response decreased over the same period. Cultured LMS showed enhanced calcium handling, including increased ability to follow pacing, higher amplitude, and faster, more stable calcium re-uptake. Structurally, LMS displayed no changes in sarcomeres, cell-cell connections, or mitochondria, despite gene expression changes in cytoskeletal and extracellular matrix-related pathways. Transcriptomic analysis revealed metabolic activation with upregulation of metabolism-related pathways. Interestingly, LMS exhibited increased expression of genes associated with early cardiac development after the culture period.LMS provide a powerful translational model for cardiovascular research, enabling the evaluation of novel therapies and fundamental studies. However, culture-induced adaptations must be carefully considered when interpreting results to ensure physiological and disease relevance.http://www.sciencedirect.com/science/article/pii/S2772976125001849Living myocardial slicesBiomimetic cultureRemodelingTranslational researchDrug developmentCardiac function |
| spellingShingle | Jort S.A. van der Geest Ernest Diez Benavente Willem B. van Ham Pieter A. Doevendans Linda W. van Laake Teun P. de Boer Vasco Sampaio-Pinto Joost P.G. Sluijter Characterization of human living myocardial slices culture-induced adaptations: a translational perspective Journal of Molecular and Cellular Cardiology Plus Living myocardial slices Biomimetic culture Remodeling Translational research Drug development Cardiac function |
| title | Characterization of human living myocardial slices culture-induced adaptations: a translational perspective |
| title_full | Characterization of human living myocardial slices culture-induced adaptations: a translational perspective |
| title_fullStr | Characterization of human living myocardial slices culture-induced adaptations: a translational perspective |
| title_full_unstemmed | Characterization of human living myocardial slices culture-induced adaptations: a translational perspective |
| title_short | Characterization of human living myocardial slices culture-induced adaptations: a translational perspective |
| title_sort | characterization of human living myocardial slices culture induced adaptations a translational perspective |
| topic | Living myocardial slices Biomimetic culture Remodeling Translational research Drug development Cardiac function |
| url | http://www.sciencedirect.com/science/article/pii/S2772976125001849 |
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