Thymosin β4 Improves Differentiation and Vascularization of EHTs
Induced pluripotent stem cells (iPSC) constitute a powerful tool to study cardiac physiology and represents a promising treatment strategy to tackle cardiac disease. However, iPSCs remain relatively immature after differentiation. Additionally, engineered heart tissue (EHT) has been investigated as...
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| Format: | Article |
| Language: | English |
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Wiley
2017-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2017/6848271 |
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| author | Tilman Ziegler Rabea Hinkel Andrea Stöhr Thomas Eschenhagen Karl-Ludwig Laugwitz Ferdinand le Noble Robert David Arne Hansen Christian Kupatt |
| author_facet | Tilman Ziegler Rabea Hinkel Andrea Stöhr Thomas Eschenhagen Karl-Ludwig Laugwitz Ferdinand le Noble Robert David Arne Hansen Christian Kupatt |
| author_sort | Tilman Ziegler |
| collection | DOAJ |
| description | Induced pluripotent stem cells (iPSC) constitute a powerful tool to study cardiac physiology and represents a promising treatment strategy to tackle cardiac disease. However, iPSCs remain relatively immature after differentiation. Additionally, engineered heart tissue (EHT) has been investigated as a therapy option in preclinical disease models with promising results, although their vascularization and functionality leave room for improvement. Thymosin β4 (Tβ4) has been shown to promote the differentiation of progenitor cell lines to cardiomyocytes while it also induces angiogenic sprouting and vascular maturation. We examined the potential impact of Tβ4 to enhance maturation of cardiomyocytes from iPSCs. Assessing the expression of transcription factors associated with cardiac differentiation, we were able to demonstrate the increased generation of cells displaying cardiomyocyte characteristics in vitro. Furthermore, we demonstrated, in a zebrafish model of embryonic vascular development, that Tβ4 is crucial for the proper execution of lymphatic and angiogenic vessel sprouting. Finally, utilizing Tβ4-transduced EHTs generated from mice genetically engineered to label endothelial cells in vitro, we show that treatment with Tβ4 promotes vascularization and contractility in EHTs, highlighting Tβ4 as a growth factor improving the formation of cardiomyocytes from iPSC and enhancing the performance of EHTs generated from neonatal cardiomyocytes. |
| format | Article |
| id | doaj-art-f03f3816f960445eb5295f342b4c8ab4 |
| institution | Kabale University |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-f03f3816f960445eb5295f342b4c8ab42025-02-03T05:47:16ZengWileyStem Cells International1687-966X1687-96782017-01-01201710.1155/2017/68482716848271Thymosin β4 Improves Differentiation and Vascularization of EHTsTilman Ziegler0Rabea Hinkel1Andrea Stöhr2Thomas Eschenhagen3Karl-Ludwig Laugwitz4Ferdinand le Noble5Robert David6Arne Hansen7Christian Kupatt8I. Medizinische Klinik und Poliklinik, Klinikum rechts der Isar, Munich, GermanyI. Medizinische Klinik und Poliklinik, Klinikum rechts der Isar, Munich, GermanyInstitut für Experimentelle Pharmakologie und Toxikologie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, GermanyInstitut für Experimentelle Pharmakologie und Toxikologie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, GermanyI. Medizinische Klinik und Poliklinik, Klinikum rechts der Isar, Munich, GermanyKarlsruher Institut für Technologie, Karlsruhe, GermanyDepartment of Cardiac Surgery, Reference and Translation Center for Cardiac Stem Cell Therapy (RTC), University of Rostock, Rostock, GermanyInstitut für Experimentelle Pharmakologie und Toxikologie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, GermanyI. Medizinische Klinik und Poliklinik, Klinikum rechts der Isar, Munich, GermanyInduced pluripotent stem cells (iPSC) constitute a powerful tool to study cardiac physiology and represents a promising treatment strategy to tackle cardiac disease. However, iPSCs remain relatively immature after differentiation. Additionally, engineered heart tissue (EHT) has been investigated as a therapy option in preclinical disease models with promising results, although their vascularization and functionality leave room for improvement. Thymosin β4 (Tβ4) has been shown to promote the differentiation of progenitor cell lines to cardiomyocytes while it also induces angiogenic sprouting and vascular maturation. We examined the potential impact of Tβ4 to enhance maturation of cardiomyocytes from iPSCs. Assessing the expression of transcription factors associated with cardiac differentiation, we were able to demonstrate the increased generation of cells displaying cardiomyocyte characteristics in vitro. Furthermore, we demonstrated, in a zebrafish model of embryonic vascular development, that Tβ4 is crucial for the proper execution of lymphatic and angiogenic vessel sprouting. Finally, utilizing Tβ4-transduced EHTs generated from mice genetically engineered to label endothelial cells in vitro, we show that treatment with Tβ4 promotes vascularization and contractility in EHTs, highlighting Tβ4 as a growth factor improving the formation of cardiomyocytes from iPSC and enhancing the performance of EHTs generated from neonatal cardiomyocytes.http://dx.doi.org/10.1155/2017/6848271 |
| spellingShingle | Tilman Ziegler Rabea Hinkel Andrea Stöhr Thomas Eschenhagen Karl-Ludwig Laugwitz Ferdinand le Noble Robert David Arne Hansen Christian Kupatt Thymosin β4 Improves Differentiation and Vascularization of EHTs Stem Cells International |
| title | Thymosin β4 Improves Differentiation and Vascularization of EHTs |
| title_full | Thymosin β4 Improves Differentiation and Vascularization of EHTs |
| title_fullStr | Thymosin β4 Improves Differentiation and Vascularization of EHTs |
| title_full_unstemmed | Thymosin β4 Improves Differentiation and Vascularization of EHTs |
| title_short | Thymosin β4 Improves Differentiation and Vascularization of EHTs |
| title_sort | thymosin β4 improves differentiation and vascularization of ehts |
| url | http://dx.doi.org/10.1155/2017/6848271 |
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