Thymosin4 Improves Differentiation and Vascularization of EHTs
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Thymosin4 Improves Differentiation and Vascularization of EHTs. / Ziegler, Tilman; Hinkel, Rabea; Stöhr, Andrea; Eschenhagen, Thomas; Laugwitz, Karl-Ludwig; le Noble, Ferdinand; David, Robert; Hansen, Arne; Kupatt, Christian.
In: Stem cells international, Vol. 2017, 01.2017, p. 6848271.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Thymosin4 Improves Differentiation and Vascularization of EHTs
AU - Ziegler, Tilman
AU - Hinkel, Rabea
AU - Stöhr, Andrea
AU - Eschenhagen, Thomas
AU - Laugwitz, Karl-Ludwig
AU - le Noble, Ferdinand
AU - David, Robert
AU - Hansen, Arne
AU - Kupatt, Christian
PY - 2017/1
Y1 - 2017/1
N2 - 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. Thymosinβ4 (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.
AB - 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. Thymosinβ4 (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.
KW - Journal Article
U2 - 10.1155/2017/6848271
DO - 10.1155/2017/6848271
M3 - SCORING: Journal article
C2 - 28191018
VL - 2017
SP - 6848271
JO - Stem Cells Int
JF - Stem Cells Int
SN - 1687-966X
ER -
