Lessons from the heart: Mirroring electrophysiological characteristics during cardiac development to in vitro differentiation of stem cell derived cardiomyocytes

Abstract The ability of human pluripotent stem cells (hPSCs) to differentiate into any cell type of the three germ layers makes them a very promising cell source for multiple purposes, including regenerative medicine, drug discovery, and as a model to study disease mechanisms and progression. One of...

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Bibliographic Details
Published in:Journal of molecular and cellular cardiology 2014-02, Vol.67, p.12-25
Main Authors: van den Heuvel, Nikki H.L, van Veen, Toon A.B, Lim, Bing, Jonsson, Malin K.B
Format: Article
Language:English
Subjects:
Cardiac development
Cardiomyocyte
Cardiovascular
Cell Differentiation
Culture Techniques
Differentiation
Electrophysiological Phenomena
Epigenomics
Heart - embryology
Heart - growth & development
Humans
Myocytes, Cardiac - cytology
Pluripotent stem cell
Pluripotent Stem Cells - cytology
Signal Transduction
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Summary:Abstract The ability of human pluripotent stem cells (hPSCs) to differentiate into any cell type of the three germ layers makes them a very promising cell source for multiple purposes, including regenerative medicine, drug discovery, and as a model to study disease mechanisms and progression. One of the first specialized cell types to be generated from hPSC was cardiomyocytes (CM), and differentiation protocols have evolved over the years and now allow for robust and large-scale production of hPSC-CM. Still, scientists are struggling to achieve the same, mainly ventricular, phenotype of the hPSC-CM in vitro as their adult counterpart in vivo. In vitro generated cardiomyocytes are generally described as fetal-like rather than adult. In this review, we compare the in vivo development of cardiomyocytes to the in vitro differentiation of hPSC into CM with focus on electrophysiology, structure and contractility. Furthermore, known epigenetic changes underlying the differences between adult human CM and CM differentiated from pluripotent stem cells are described. This should provide the reader with an extensive overview of the current status of human stem cell-derived cardiomyocyte phenotype and function. Additionally, the reader will gain insight into the underlying signaling pathways and mechanisms responsible for cardiomyocyte development.
ISSN:0022-2828
1095-8584
DOI:10.1016/j.yjmcc.2013.12.011