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The effect of microgrooved culture substrates on calcium cycling of cardiac myocytes derived from human induced pluripotent stem cells

The effect of microgrooved culture substrates on calcium cycling of cardiac myocytes derived from human induced pluripotent stem cells
The effect of microgrooved culture substrates on calcium cycling of cardiac myocytes derived from human induced pluripotent stem cells
Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) have been widely proposed as in vitro models of myocardial physiology and disease. A significant obstacle, however, is their immature phenotype. We hypothesised that Ca2+ cycling of iPSC-CM is influenced by culture conditions and can be manipulated to obtain a more mature cellular behaviour. To test this hypothesis we seeded iPSC-CM onto fibronectin coated microgrooved polydimethylsiloxane (PDMS) scaffolds fabricated using photolithography, or onto unstructured PDMS membrane. After two weeks in culture, the structure and function of iPSC-CM were studied. PDMS microgrooved culture substrates brought about cellular alignment (p < 0.0001) and more organised sarcomere. The Ca2+ cycling properties of iPSC-CM cultured on these substrates were significantly altered with a shorter time to peak amplitude (p = 0.0002 at 1 Hz), and more organised sarcoplasmic reticulum (SR) Ca2+ release in response to caffeine (p < 0.0001), suggesting improved SR Ca2+ cycling. These changes were not associated with modifications in gene expression. Whilst structured tissue culture may make iPSC-CM more representative of adult myocardium, further construct development and characterisation is required to optimise iPSC-CM as a model of adult myocardium.
0142-9612
2399-2411
Rao, Christopher
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Prodromakis, Themistoklis
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Kolker, Ljudmila
6e39d34f-0989-4174-80de-d473d84b041a
Chaudhry, Umar A.R.
c7e17ed4-0378-4c91-964b-59e0b594cd58
Trantidou, Tatiana
d5672813-459c-47da-9de0-843449d3ce25
Sridhar, Arun
9a737f08-b742-4425-a329-0c17ecdd35b8
Weekes, Claire
e951d795-0f20-423b-b1ef-edfb696d177a
Camelliti, Patrizia
4640b1ee-33f7-46d6-ac7f-e48166a6d8f2
Harding, Sian E.
7533fcea-2cc2-4d3c-a341-ad3fcae57205
Darzi, Ara
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Yacoub, Magdi H.
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Athanasiou, Thanos
c72f0f83-e61a-42e7-aa01-f65faf84cb39
Terracciano, Cesare M.
f8732401-1482-42aa-a8a6-9485b345a065
Rao, Christopher
42b68144-8bc1-4db5-9e7e-025602ef75f0
Prodromakis, Themistoklis
d58c9c10-9d25-4d22-b155-06c8437acfbf
Kolker, Ljudmila
6e39d34f-0989-4174-80de-d473d84b041a
Chaudhry, Umar A.R.
c7e17ed4-0378-4c91-964b-59e0b594cd58
Trantidou, Tatiana
d5672813-459c-47da-9de0-843449d3ce25
Sridhar, Arun
9a737f08-b742-4425-a329-0c17ecdd35b8
Weekes, Claire
e951d795-0f20-423b-b1ef-edfb696d177a
Camelliti, Patrizia
4640b1ee-33f7-46d6-ac7f-e48166a6d8f2
Harding, Sian E.
7533fcea-2cc2-4d3c-a341-ad3fcae57205
Darzi, Ara
5a4bc779-f6b1-44c8-ae23-eb289b59ad27
Yacoub, Magdi H.
834a5d93-f7a4-4efc-9bd0-41901f8b38e9
Athanasiou, Thanos
c72f0f83-e61a-42e7-aa01-f65faf84cb39
Terracciano, Cesare M.
f8732401-1482-42aa-a8a6-9485b345a065

Rao, Christopher, Prodromakis, Themistoklis, Kolker, Ljudmila, Chaudhry, Umar A.R., Trantidou, Tatiana, Sridhar, Arun, Weekes, Claire, Camelliti, Patrizia, Harding, Sian E., Darzi, Ara, Yacoub, Magdi H., Athanasiou, Thanos and Terracciano, Cesare M. (2013) The effect of microgrooved culture substrates on calcium cycling of cardiac myocytes derived from human induced pluripotent stem cells. Biomaterials, 34 (10), 2399-2411. (doi:10.1016/j.biomaterials.2012.11.055).

Record type: Article

Abstract

Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) have been widely proposed as in vitro models of myocardial physiology and disease. A significant obstacle, however, is their immature phenotype. We hypothesised that Ca2+ cycling of iPSC-CM is influenced by culture conditions and can be manipulated to obtain a more mature cellular behaviour. To test this hypothesis we seeded iPSC-CM onto fibronectin coated microgrooved polydimethylsiloxane (PDMS) scaffolds fabricated using photolithography, or onto unstructured PDMS membrane. After two weeks in culture, the structure and function of iPSC-CM were studied. PDMS microgrooved culture substrates brought about cellular alignment (p < 0.0001) and more organised sarcomere. The Ca2+ cycling properties of iPSC-CM cultured on these substrates were significantly altered with a shorter time to peak amplitude (p = 0.0002 at 1 Hz), and more organised sarcoplasmic reticulum (SR) Ca2+ release in response to caffeine (p < 0.0001), suggesting improved SR Ca2+ cycling. These changes were not associated with modifications in gene expression. Whilst structured tissue culture may make iPSC-CM more representative of adult myocardium, further construct development and characterisation is required to optimise iPSC-CM as a model of adult myocardium.

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Published date: March 2013
Organisations: Nanoelectronics and Nanotechnology

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Local EPrints ID: 351531
URI: https://eprints.soton.ac.uk/id/eprint/351531
ISSN: 0142-9612
PURE UUID: e81ef3cf-9dca-447f-814d-c2c320a88679

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Date deposited: 23 Apr 2013 10:26
Last modified: 18 Jul 2017 04:25

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Contributors

Author: Christopher Rao
Author: Ljudmila Kolker
Author: Umar A.R. Chaudhry
Author: Tatiana Trantidou
Author: Arun Sridhar
Author: Claire Weekes
Author: Patrizia Camelliti
Author: Sian E. Harding
Author: Ara Darzi
Author: Magdi H. Yacoub
Author: Thanos Athanasiou
Author: Cesare M. Terracciano

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