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.
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DOI：
10.1016/j.biomaterials.2012.11.055
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发表时间：
2013-03
期刊：
影响因子：
14
通讯作者：
Terracciano, Cesare M.
中科院分区：
文献类型：
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作者：
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;Terracciano, Cesare M.
关键词：
诱导多能干细胞衍生的心肌细胞（iPSC-CM）已被广泛提出作为心肌生理和疾病的体外模型。然而，一个重要的障碍是它们不成熟的表型。我们假设iPSC-CM的Ca2+循环受到培养条件的影响，可以操纵以获得更成熟的细胞行为。为了验证这一假设，我们将iPSC-CM植入到光刻技术制备的纤维连接蛋白包被的微槽聚二甲基硅氧烷（PDMS）支架或非结构化PDMS膜上。培养2周后，研究iPSC-CM的结构和功能。PDMS微槽培养基质带来细胞排列（p < 0.0001）和更有组织的肌节。在这些基质上培养的iPSC-CM的Ca2+循环特性显著改变，达到峰值振幅的时间更短（p = 0.0002 at 1 Hz），并且更有组织的肌浆网（SR） Ca2+释放响应于咖啡因（p < 0.0001），表明SR Ca2+循环改善。这些变化与基因表达的改变无关。虽然结构化组织培养可以使iPSC-CM更能代表成人心肌，但需要进一步的构建开发和表征来优化iPSC-CM作为成人心肌模型。
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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影响因子：
2.4
作者：
Jacot JG;Martin JC;Hunt DL
通讯作者：
Hunt DL
影响因子：
14
作者：
Feinberg, Adam W.;Alford, Patrick W.;Jin, Hongwei;Ripplinger, Crystal M.;Werdich, Andreas A.;Sheehy, Sean P.;Grosberg, Anna;Parker, Kevin Kit
通讯作者：
Parker, Kevin Kit
分层结构影响工程心肌的钙动力学。
DOI：
10.1258/ebm.2010.010239
发表时间：
2011-03
期刊：
Experimental biology and medicine (Maywood, N.J.)
影响因子：
--
作者：
Pong T;Adams WJ;Bray MA;Feinberg AW;Sheehy SP;Werdich AA;Parker KK
通讯作者：
Parker KK
影响因子：
4.1
作者：
Boudou, Thomas;Legant, Wesley R.;Chen, Christopher S.
通讯作者：
Chen, Christopher S.
影响因子：
64.8
作者：
通讯作者：
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