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Stem Cells International
Volume 2017, Article ID 6848271, 10 pages
Research Article

Thymosin β4 Improves Differentiation and Vascularization of EHTs

1I. Medizinische Klinik und Poliklinik, Klinikum rechts der Isar, Munich, Germany
2German Center for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany
3Institute for Cardiovascular Prevention, Ludwig Maximilians University, Munich, Germany
4Institut für Experimentelle Pharmakologie und Toxikologie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
5Karlsruher Institut für Technologie, Karlsruhe, Germany
6Department of Cardiac Surgery, Reference and Translation Center for Cardiac Stem Cell Therapy (RTC), University of Rostock, Rostock, Germany
7German Center for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Lübeck, Hamburg, Germany

Correspondence should be addressed to Christian Kupatt; ed.mut@ttapuk.naitsirhc

Received 23 September 2016; Accepted 7 November 2016; Published 16 January 2017

Academic Editor: Arnon Blum

Copyright © 2017 Tilman Ziegler et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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.