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

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.

Original languageEnglish
Pages (from-to)2399-2411
Number of pages13
JournalBiomaterials
Volume34
Issue number10
Early online date20 Dec 2012
DOIs
Publication statusPublished - Mar 2013

Keywords / Materials (for Non-textual outputs)

  • Calcium cycling
  • Cardiac tissue engineering
  • Electrophysiology
  • Micropatterning
  • Polydimethylsiloxane
  • Stem cells

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