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

Rao, C, Prodromakis, T, Kolker, L, Chaudhry, UA, Trantidou, T, Sridhar, A, Weekes, C, Camelliti, P, Harding, SE, Darzi, A , Yacoub, MH, Athanasiou, T and Terracciano, CM (2013) The effect of microgrooved culture substrates on calcium cycling of cardiac myocytes derived from human induced pluripotent stem cells. Biomaterials, 34 (10). pp. 2399-2411.

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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 Ca(2+) 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 Ca(2+) 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) Ca(2+) release in response to caffeine (p < 0.0001), suggesting improved SR Ca(2+) 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.

Item Type: Article
Authors :
NameEmailORCID
Rao, CUNSPECIFIEDUNSPECIFIED
Prodromakis, TUNSPECIFIEDUNSPECIFIED
Kolker, LUNSPECIFIEDUNSPECIFIED
Chaudhry, UAUNSPECIFIEDUNSPECIFIED
Trantidou, TUNSPECIFIEDUNSPECIFIED
Sridhar, AUNSPECIFIEDUNSPECIFIED
Weekes, CUNSPECIFIEDUNSPECIFIED
Camelliti, Pp.camelliti@surrey.ac.ukUNSPECIFIED
Harding, SEUNSPECIFIEDUNSPECIFIED
Darzi, AUNSPECIFIEDUNSPECIFIED
Yacoub, MHUNSPECIFIEDUNSPECIFIED
Athanasiou, TUNSPECIFIEDUNSPECIFIED
Terracciano, CMUNSPECIFIEDUNSPECIFIED
Date : March 2013
Identification Number : 10.1016/j.biomaterials.2012.11.055
Uncontrolled Keywords : Dimethylpolysiloxanes, Electrophysiology, Humans, Induced Pluripotent Stem Cells, Models, Theoretical, Myocytes, Cardiac
Related URLs :
Depositing User : Symplectic Elements
Date Deposited : 17 May 2017 09:59
Last Modified : 17 May 2017 14:46
URI: http://epubs.surrey.ac.uk/id/eprint/825957

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