Induced pluripotent stem cell derived cardiac models: effects of Thymosin β4

ABSTRACT

Introduction: The establishment of induced pluripotent stem cells (iPSCs) and cardiomyocytes differentiated from them generated a new platform to study pathophysiological processes and to generate drug screening platforms and iPSC-derived tissues as therapeutic agents. Although major advances have been made in iPSC-reprogramming, cardiac differentiation and EHT production, reprogramming efficiency and the maturity of iPSC-CMs need to be further improved.

Areas covered: In this review, the authors summarize the current state of the field of iPSC research, the methodology of cardiac differentiation of iPSCs, the use of iPSC-CMs as disease models and toxicity screening platforms, and the potential of EHTs as therapeutic agents. The authors furthermore highlight the mechanisms by which Thymosin β4 might enhance the production of iPSC-CMs and EHTs to improve their maturity and performance.

Expert Opinion: iPSCs derived cardiomyocytes and EHTs represent a still young research field with many problems and pitfalls that need to be resolved to realize the full potential of iPSC-CMs and EHTs. Given that Thymosin β4 directly enhances cardiac differentiation while also promoting angiogenic sprouting and vessel maturation, Tβ4 might be of particular interest as a novel agent in tackling the difficulty of iPSC-CMs and engineered heart tissue grafts.

KEYWORDS:

• EHT
• iPSC
• pluripotent stem cells
• Thymosin β4
• Tb4

Acknowledgments

Part of the content of this paper was presented at Fifth International Symposium on Thymosins in Health and Disease and is part of a supplement issue funded by SciClone Pharmaceuticals.

Article highlights

• Induced pluripotent stem cells (iPSCs) can be produced by reprogramming of somatic cells via the overexpression of transcription factors

• Retroviral overexpression of the Yamanaka factors (SOX2, OCT3/4, c-MYC, KLF4) represents the current standard in reprogramming

• Differentiation of iPSCs into cardiomyocytes can be achieved by cultivation in specelized media and on varying extracellular matrix components

• iPS-derived cardiomyocytes allow an approximation to adult cardiomyocytes, allowing for the in-depth study of human cardiomyocyte physiology

• Engineered heart tissue grafts (EHTs) from iPSCs further mature iPS cells and have been used to treat cardiac pathologies in animal experiments

• Thymosin β4 promotes differentiation of iPSCs to cardiomyocytes and improves EHT maturation and vasculariation

This box summarizes key points contained in the article.

Declaration of Interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

RH and CK have received funding from the German Ministry of Education and Research (BMBF, GENEVA) and Else-Kroner-Fresenius foundation. This paper has been published as part of a supplement issue covering the proceedings of the Fifth International Symposium on Thymosins in Health and Disease and is funded by SciClone Pharmaceuticals.