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Embryonic stem cell-derived cardiomyocytes as a model to study fetal arrhythmia related to maternal disease

Embryonic stem cell-derived cardiomyocytes (ESC-CM) have many of the phenotypic properties of authentic cardiomyocytes, and great interest has been shown in their possibilities for modelling human disease. Obstetric cholestasis affects 1 in 200 pregnant women in the United Kingdom. It is characteriz...

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Autores principales: Kadir, Siti H Sheikh Abdul, Ali, Nadire N, Mioulane, Maxime, Brito-Martins, Marta, Abu-Hayyeh, Shadi, Foldes, Gabor, Moshkov, Alexey V, Williamson, Catherine, Harding, Sian E, Gorelik, Julia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Ltd 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4516522/
https://www.ncbi.nlm.nih.gov/pubmed/19438812
http://dx.doi.org/10.1111/j.1582-4934.2009.00741.x
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author Kadir, Siti H Sheikh Abdul
Ali, Nadire N
Mioulane, Maxime
Brito-Martins, Marta
Abu-Hayyeh, Shadi
Foldes, Gabor
Moshkov, Alexey V
Williamson, Catherine
Harding, Sian E
Gorelik, Julia
author_facet Kadir, Siti H Sheikh Abdul
Ali, Nadire N
Mioulane, Maxime
Brito-Martins, Marta
Abu-Hayyeh, Shadi
Foldes, Gabor
Moshkov, Alexey V
Williamson, Catherine
Harding, Sian E
Gorelik, Julia
author_sort Kadir, Siti H Sheikh Abdul
collection PubMed
description Embryonic stem cell-derived cardiomyocytes (ESC-CM) have many of the phenotypic properties of authentic cardiomyocytes, and great interest has been shown in their possibilities for modelling human disease. Obstetric cholestasis affects 1 in 200 pregnant women in the United Kingdom. It is characterized by raised serum bile acids and complicated by premature delivery and unexplained fetal death at late gestation. It has been suggested that the fetal death is caused by the enhanced arrhythmogenic effect of bile acids in the fetal heart, and shown that neonatal susceptibility to bile acid-induced arrhythmia is lost in the adult rat cardiomyocyte. However, the mechanisms of the observed bile acid effects are not fully understood and their in vivo study in human beings is difficult. Here we use ESC-CM from both human and mouse ESCs to test our proposal that immature cardiomyocytes are more susceptible to the effect of raised bile acids than mature ones. We show that early ESC-CM exhibit bile acid-induced disruption of rhythm, depression of contraction and desynchronization of cell coupling. In both species the ESC-CM become resistant to these arrhythmias as the cells mature, and this develops in line with the respective gestational periods of mouse and human. This represents the first demonstration of the use of ESC-CM as a model system for human cardiac pathology, and opens the way for both investigation of mechanisms and a high throughput screen for drug discovery.
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spelling pubmed-45165222015-08-03 Embryonic stem cell-derived cardiomyocytes as a model to study fetal arrhythmia related to maternal disease Kadir, Siti H Sheikh Abdul Ali, Nadire N Mioulane, Maxime Brito-Martins, Marta Abu-Hayyeh, Shadi Foldes, Gabor Moshkov, Alexey V Williamson, Catherine Harding, Sian E Gorelik, Julia J Cell Mol Med Disease Models Embryonic stem cell-derived cardiomyocytes (ESC-CM) have many of the phenotypic properties of authentic cardiomyocytes, and great interest has been shown in their possibilities for modelling human disease. Obstetric cholestasis affects 1 in 200 pregnant women in the United Kingdom. It is characterized by raised serum bile acids and complicated by premature delivery and unexplained fetal death at late gestation. It has been suggested that the fetal death is caused by the enhanced arrhythmogenic effect of bile acids in the fetal heart, and shown that neonatal susceptibility to bile acid-induced arrhythmia is lost in the adult rat cardiomyocyte. However, the mechanisms of the observed bile acid effects are not fully understood and their in vivo study in human beings is difficult. Here we use ESC-CM from both human and mouse ESCs to test our proposal that immature cardiomyocytes are more susceptible to the effect of raised bile acids than mature ones. We show that early ESC-CM exhibit bile acid-induced disruption of rhythm, depression of contraction and desynchronization of cell coupling. In both species the ESC-CM become resistant to these arrhythmias as the cells mature, and this develops in line with the respective gestational periods of mouse and human. This represents the first demonstration of the use of ESC-CM as a model system for human cardiac pathology, and opens the way for both investigation of mechanisms and a high throughput screen for drug discovery. John Wiley & Sons, Ltd 2009-09 2009-03-06 /pmc/articles/PMC4516522/ /pubmed/19438812 http://dx.doi.org/10.1111/j.1582-4934.2009.00741.x Text en © 2009 The Authors Journal compilation © 2009 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd
spellingShingle Disease Models
Kadir, Siti H Sheikh Abdul
Ali, Nadire N
Mioulane, Maxime
Brito-Martins, Marta
Abu-Hayyeh, Shadi
Foldes, Gabor
Moshkov, Alexey V
Williamson, Catherine
Harding, Sian E
Gorelik, Julia
Embryonic stem cell-derived cardiomyocytes as a model to study fetal arrhythmia related to maternal disease
title Embryonic stem cell-derived cardiomyocytes as a model to study fetal arrhythmia related to maternal disease
title_full Embryonic stem cell-derived cardiomyocytes as a model to study fetal arrhythmia related to maternal disease
title_fullStr Embryonic stem cell-derived cardiomyocytes as a model to study fetal arrhythmia related to maternal disease
title_full_unstemmed Embryonic stem cell-derived cardiomyocytes as a model to study fetal arrhythmia related to maternal disease
title_short Embryonic stem cell-derived cardiomyocytes as a model to study fetal arrhythmia related to maternal disease
title_sort embryonic stem cell-derived cardiomyocytes as a model to study fetal arrhythmia related to maternal disease
topic Disease Models
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4516522/
https://www.ncbi.nlm.nih.gov/pubmed/19438812
http://dx.doi.org/10.1111/j.1582-4934.2009.00741.x
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