Theranostics 2017; 7(7):2078-2091. doi:10.7150/thno.19390

Research Paper

Metabolomics Identifies Metabolic Markers of Maturation in Human Pluripotent Stem Cell-Derived Cardiomyocytes

Vijesh J. Bhute1*, Xiaoping Bao1*, Kaitlin K. Dunn1, Kylie R. Knutson1, Eric C. McCurry1, Gyuhyung Jin1, Wei-Hua Lee2, Sarah Lewis2, Akihiro Ikeda2, Sean P. Palecek1✉

1. Department of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, WI 53706, USA;
2. Department of Medical Genetics, University of Wisconsin-Madison, Madison, WI 53706, USA.
* These authors contributed equally to this work.

Abstract

Cardiovascular disease is a leading cause of death worldwide. Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) hold immense clinical potential and recent studies have enabled generation of virtually pure hPSC-CMs with high efficiency in chemically defined and xeno-free conditions. Despite these advances, hPSC-CMs exhibit an immature phenotype and are arrhythmogenic in vivo, necessitating development of strategies to mature these cells. hPSC-CMs undergo significant metabolic alterations during differentiation and maturation. A detailed analysis of the metabolic changes accompanying maturation of hPSC-CMs may prove useful in identifying new strategies to expedite hPSC-CM maturation and also may provide biomarkers for testing or validating hPSC-CM maturation. In this study we identified global metabolic changes which take place during long-term culture and maturation of hPSC-CMs derived from three different hPSC lines. We have identified several metabolic pathways, including phospholipid metabolism and pantothenate and Coenzyme A metabolism, which showed significant enrichment upon maturation in addition to fatty acid oxidation and metabolism. We also identified increases in glycerophosphocholine and the glycerophosphocholine:phosphocholine ratio as potential metabolic biomarkers of maturation. These biomarkers were also affected in a similar manner during murine heart development in vivo. These results support that hPSC-CM maturation is associated with extensive metabolic changes in metabolic network utilization and understanding the roles of these metabolic changes has the potential to develop novel approaches to monitor and expedite hPSC-CM maturation.

Keywords: Human Pluripotent Stem Cells, Cardiomyocytes, Maturation, Metabolomics, Biomarkers.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
How to cite this article:
Bhute VJ, Bao X, Dunn KK, Knutson KR, McCurry EC, Jin G, Lee WH, Lewis S, Ikeda A, Palecek SP. Metabolomics Identifies Metabolic Markers of Maturation in Human Pluripotent Stem Cell-Derived Cardiomyocytes. Theranostics 2017; 7(7):2078-2091. doi:10.7150/thno.19390. Available from http://www.thno.org/v07p2078.htm