Thymosin β 4 Improves Differentiation and Vascularization of EHTs

Ziegler T, Hinkel R, Stohr A, Eschenhagen T, Laugwitz KL, Le Noble F, David R, Hansen A, Kupatt C (2017)

Publication Type: Journal article

Publication year: 2017

Journal

Stem Cells International Hindawi Publishing Corporation

Book Volume: 2017

Article Number: 6848271

DOI: 10.1155/2017/6848271

Abstract

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.

Involved external institutions

Klinikum rechts der Isar DE Germany (DE) Universitätsklinikum Hamburg-Eppendorf (UKE) DE Germany (DE) Karlsruhe Institute of Technology (KIT) DE Germany (DE) Universität Rostock DE Germany (DE)

How to cite

APA:

Ziegler, T., Hinkel, R., Stohr, A., Eschenhagen, T., Laugwitz, K.-L., Le Noble, F.,... Kupatt, C. (2017). Thymosin β 4 Improves Differentiation and Vascularization of EHTs. Stem Cells International, 2017. https://doi.org/10.1155/2017/6848271

MLA:

Ziegler, Tilman, et al. "Thymosin β 4 Improves Differentiation and Vascularization of EHTs." Stem Cells International 2017 (2017).

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