期刊
BIOMATERIALS
卷 34, 期 10, 页码 2399-2411出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2012.11.055
关键词
Calcium cycling; Cardiac tissue engineering; Electrophysiology; Micropatterning; Polydimethylsiloxane; Stem cells
资金
- Wellcome Trust Clinical Research PhD studentship
- Imperial College Fellowship
- British Heart Foundation [RG/11/19/29264] Funding Source: researchfish
- Medical Research Council [MR/L012618/1] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0510-10186] Funding Source: researchfish
- MRC [MR/L012618/1] Funding Source: UKRI
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. (C) 2012 Elsevier Ltd. All rights reserved.
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