Steps toward Maturation of Embryonic Stem Cell-Derived Cardiomyocytes by Defined Physical Signals
Cardiovascular disease remains a leading cause of mortality and morbidity worldwide. Embryonic stem cell-derived cardiomyocytes (ESC-CMs) may offer significant advances in creating in vitro cardiac tissues for disease modeling, drug testing, and elucidating developmental processes; however, the indu...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2017-07-01
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| Series: | Stem Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213671117301753 |
| _version_ | 1818827430707593216 |
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| author | Nian Shen Anne Knopf Claas Westendorf Udo Kraushaar Julia Riedl Hannah Bauer Simone Pöschel Shannon Lee Layland Monika Holeiter Stefan Knolle Eva Brauchle Ali Nsair Svenja Hinderer Katja Schenke-Layland |
| author_facet | Nian Shen Anne Knopf Claas Westendorf Udo Kraushaar Julia Riedl Hannah Bauer Simone Pöschel Shannon Lee Layland Monika Holeiter Stefan Knolle Eva Brauchle Ali Nsair Svenja Hinderer Katja Schenke-Layland |
| author_sort | Nian Shen |
| collection | DOAJ |
| description | Cardiovascular disease remains a leading cause of mortality and morbidity worldwide. Embryonic stem cell-derived cardiomyocytes (ESC-CMs) may offer significant advances in creating in vitro cardiac tissues for disease modeling, drug testing, and elucidating developmental processes; however, the induction of ESCs to a more adult-like CM phenotype remains challenging. In this study, we developed a bioreactor system to employ pulsatile flow (1.48 mL/min), cyclic strain (5%), and extended culture time to improve the maturation of murine and human ESC-CMs. Dynamically-cultured ESC-CMs showed an increased expression of cardiac-associated proteins and genes, cardiac ion channel genes, as well as increased SERCA activity and a Raman fingerprint with the presence of maturation-associated peaks similar to primary CMs. We present a bioreactor platform that can serve as a foundation for the development of human-based cardiac in vitro models to verify drug candidates, and facilitates the study of cardiovascular development and disease. |
| first_indexed | 2024-12-19T00:43:26Z |
| format | Article |
| id | doaj.art-51a74827056543bc98979ec6f82bf94e |
| institution | Directory Open Access Journal |
| issn | 2213-6711 |
| language | English |
| last_indexed | 2024-12-19T00:43:26Z |
| publishDate | 2017-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Stem Cell Reports |
| spelling | doaj.art-51a74827056543bc98979ec6f82bf94e2022-12-21T20:44:24ZengElsevierStem Cell Reports2213-67112017-07-019112213510.1016/j.stemcr.2017.04.021Steps toward Maturation of Embryonic Stem Cell-Derived Cardiomyocytes by Defined Physical SignalsNian Shen0Anne Knopf1Claas Westendorf2Udo Kraushaar3Julia Riedl4Hannah Bauer5Simone Pöschel6Shannon Lee Layland7Monika Holeiter8Stefan Knolle9Eva Brauchle10Ali Nsair11Svenja Hinderer12Katja Schenke-Layland13Department of Cell and Tissue Engineering, Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB, Stuttgart 70569, GermanyDepartment of Cell and Tissue Engineering, Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB, Stuttgart 70569, GermanyDepartment of Cell and Tissue Engineering, Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB, Stuttgart 70569, GermanyDepartment of Cell Biology, Electrophysiology, Natural and Medical Sciences Institute, University of Tübingen, Reutlingen 72770, GermanyDepartment of Cell and Tissue Engineering, Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB, Stuttgart 70569, GermanyDepartment of Women's Health, Research Institute of Women's Health, University Hospital of the Eberhard Karls University Tübingen, Tübingen 72076, GermanyDepartment of Women's Health, Research Institute of Women's Health, University Hospital of the Eberhard Karls University Tübingen, Tübingen 72076, GermanyDepartment of Cell and Tissue Engineering, Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB, Stuttgart 70569, GermanyDepartment of Cell and Tissue Engineering, Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB, Stuttgart 70569, GermanyDepartment of Cell and Tissue Engineering, Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB, Stuttgart 70569, GermanyDepartment of Cell and Tissue Engineering, Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB, Stuttgart 70569, GermanyDepartment of Medicine/Cardiology, Cardiovascular Research Laboratories (CVRL), David Geffen School of Medicine, University of California Los Angeles (UCLA), Los Angeles, CA 90095, USADepartment of Cell and Tissue Engineering, Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB, Stuttgart 70569, GermanyDepartment of Cell and Tissue Engineering, Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB, Stuttgart 70569, GermanyCardiovascular disease remains a leading cause of mortality and morbidity worldwide. Embryonic stem cell-derived cardiomyocytes (ESC-CMs) may offer significant advances in creating in vitro cardiac tissues for disease modeling, drug testing, and elucidating developmental processes; however, the induction of ESCs to a more adult-like CM phenotype remains challenging. In this study, we developed a bioreactor system to employ pulsatile flow (1.48 mL/min), cyclic strain (5%), and extended culture time to improve the maturation of murine and human ESC-CMs. Dynamically-cultured ESC-CMs showed an increased expression of cardiac-associated proteins and genes, cardiac ion channel genes, as well as increased SERCA activity and a Raman fingerprint with the presence of maturation-associated peaks similar to primary CMs. We present a bioreactor platform that can serve as a foundation for the development of human-based cardiac in vitro models to verify drug candidates, and facilitates the study of cardiovascular development and disease.http://www.sciencedirect.com/science/article/pii/S2213671117301753bioreactorpluripotent stem cellscardiovascularflowcyclic surface strainRaman spectroscopy |
| spellingShingle | Nian Shen Anne Knopf Claas Westendorf Udo Kraushaar Julia Riedl Hannah Bauer Simone Pöschel Shannon Lee Layland Monika Holeiter Stefan Knolle Eva Brauchle Ali Nsair Svenja Hinderer Katja Schenke-Layland Steps toward Maturation of Embryonic Stem Cell-Derived Cardiomyocytes by Defined Physical Signals Stem Cell Reports bioreactor pluripotent stem cells cardiovascular flow cyclic surface strain Raman spectroscopy |
| title | Steps toward Maturation of Embryonic Stem Cell-Derived Cardiomyocytes by Defined Physical Signals |
| title_full | Steps toward Maturation of Embryonic Stem Cell-Derived Cardiomyocytes by Defined Physical Signals |
| title_fullStr | Steps toward Maturation of Embryonic Stem Cell-Derived Cardiomyocytes by Defined Physical Signals |
| title_full_unstemmed | Steps toward Maturation of Embryonic Stem Cell-Derived Cardiomyocytes by Defined Physical Signals |
| title_short | Steps toward Maturation of Embryonic Stem Cell-Derived Cardiomyocytes by Defined Physical Signals |
| title_sort | steps toward maturation of embryonic stem cell derived cardiomyocytes by defined physical signals |
| topic | bioreactor pluripotent stem cells cardiovascular flow cyclic surface strain Raman spectroscopy |
| url | http://www.sciencedirect.com/science/article/pii/S2213671117301753 |
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