Distinct carbon sources affect structural and functional maturation of cardiomyocytes derived from human pluripotent stem cells

Abstract The immature phenotype of human pluripotent stem cell derived cardiomyocytes (hPSC-CMs) constrains their potential in cell therapy and drug testing. In this study, we report that shifting hPSC-CMs from glucose-containing to galactose- and fatty acid-containing medium promotes their fast mat...

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Autores principales:	Cláudia Correia, Alexey Koshkin, Patrícia Duarte, Dongjian Hu, Ana Teixeira, Ibrahim Domian, Margarida Serra, Paula M. Alves
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9c935c36e30c479f9006244f67d812d0
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spelling	oai:doaj.org-article:9c935c36e30c479f9006244f67d812d02021-12-02T11:53:07ZDistinct carbon sources affect structural and functional maturation of cardiomyocytes derived from human pluripotent stem cells10.1038/s41598-017-08713-42045-2322https://doaj.org/article/9c935c36e30c479f9006244f67d812d02017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08713-4https://doaj.org/toc/2045-2322Abstract The immature phenotype of human pluripotent stem cell derived cardiomyocytes (hPSC-CMs) constrains their potential in cell therapy and drug testing. In this study, we report that shifting hPSC-CMs from glucose-containing to galactose- and fatty acid-containing medium promotes their fast maturation into adult-like CMs with higher oxidative metabolism, transcriptional signatures closer to those of adult ventricular tissue, higher myofibril density and alignment, improved calcium handling, enhanced contractility, and more physiological action potential kinetics. Integrated “-Omics” analyses showed that addition of galactose to culture medium improves total oxidative capacity of the cells and ameliorates fatty acid oxidation avoiding the lipotoxicity that results from cell exposure to high fatty acid levels. This study provides an important link between substrate utilization and functional maturation of hPSC-CMs facilitating the application of this promising cell type in clinical and preclinical applications.Cláudia CorreiaAlexey KoshkinPatrícia DuarteDongjian HuAna TeixeiraIbrahim DomianMargarida SerraPaula M. AlvesNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-17 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Cláudia Correia Alexey Koshkin Patrícia Duarte Dongjian Hu Ana Teixeira Ibrahim Domian Margarida Serra Paula M. Alves Distinct carbon sources affect structural and functional maturation of cardiomyocytes derived from human pluripotent stem cells
description	Abstract The immature phenotype of human pluripotent stem cell derived cardiomyocytes (hPSC-CMs) constrains their potential in cell therapy and drug testing. In this study, we report that shifting hPSC-CMs from glucose-containing to galactose- and fatty acid-containing medium promotes their fast maturation into adult-like CMs with higher oxidative metabolism, transcriptional signatures closer to those of adult ventricular tissue, higher myofibril density and alignment, improved calcium handling, enhanced contractility, and more physiological action potential kinetics. Integrated “-Omics” analyses showed that addition of galactose to culture medium improves total oxidative capacity of the cells and ameliorates fatty acid oxidation avoiding the lipotoxicity that results from cell exposure to high fatty acid levels. This study provides an important link between substrate utilization and functional maturation of hPSC-CMs facilitating the application of this promising cell type in clinical and preclinical applications.
format	article
author	Cláudia Correia Alexey Koshkin Patrícia Duarte Dongjian Hu Ana Teixeira Ibrahim Domian Margarida Serra Paula M. Alves
author_facet	Cláudia Correia Alexey Koshkin Patrícia Duarte Dongjian Hu Ana Teixeira Ibrahim Domian Margarida Serra Paula M. Alves
author_sort	Cláudia Correia
title	Distinct carbon sources affect structural and functional maturation of cardiomyocytes derived from human pluripotent stem cells
title_short	Distinct carbon sources affect structural and functional maturation of cardiomyocytes derived from human pluripotent stem cells
title_full	Distinct carbon sources affect structural and functional maturation of cardiomyocytes derived from human pluripotent stem cells
title_fullStr	Distinct carbon sources affect structural and functional maturation of cardiomyocytes derived from human pluripotent stem cells
title_full_unstemmed	Distinct carbon sources affect structural and functional maturation of cardiomyocytes derived from human pluripotent stem cells
title_sort	distinct carbon sources affect structural and functional maturation of cardiomyocytes derived from human pluripotent stem cells
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/9c935c36e30c479f9006244f67d812d0
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_version_	1718394881814036480

Distinct carbon sources affect structural and functional maturation of cardiomyocytes derived from human pluripotent stem cells

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