Enhanced Human-Induced Pluripotent Stem Cell Derived Cardiomyocyte Maturation Using a Dual Microgradient Substrate.
Enhanced Human-Induced Pluripotent Stem Cell Derived Cardiomyocyte Maturation Using a Dual Microgradient Substrate.
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增强了人类诱导的多能干细胞衍生的心肌细胞的成熟，使用双重微型底物成熟。
DOI：
10.1021/acsbiomaterials.6b00426
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发表时间：
2016-12-12
影响因子：
5.8
通讯作者：
Gadegaard, N.
中科院分区：
文献类型：
--
作者：
Huethorst, E.;Hortigon, M.;Zamora-Rodriguez, V.;Reynolds, P. M.;Burton, F.;Smith, G.;Gadegaard, N.
人诱导多能干细胞来源的心肌细胞(hiPSC-CM)为心脏研究提供了许多可能性，但它们表现出不成熟的表型，这影响了实验结果。我们研究的目的是研究地形梯度衬底对商用HiPSC-CM的形态和功能的影响。衬底上微槽的横向尺寸在一轴上的8μm槽之间的间距为8到100μm之间，在另一轴上的深度从∼5 nm到∼1μm。根据制造商的方案，将细胞均匀种植在基质上。在第4天和第10天，测量HiPSC-CM的偏心率、伸长率、取向、肌节长度(SL)和收缩性能。只有最深和最宽的区域(宽8-30μm和深0.85-1μm)的hPSC-CM的比例显著高于对照组(分别为15.8±5.0%、3.4±2.7%和10.6±1.1%)，偏心率(31.3±6.4%)、伸长率(10.4±4.3%)和取向(<；10°)(32.1±2.7%)均高于对照组(分别为15.8±5.0%、3.4±2.7%和10.6±1.1%)。此外，在刺激诱导的收缩中，与未延长的细胞(200ms)相比，抽动的松弛阶段延长(400ms)。这些发现支持使用双微梯度底物来研究刺激HiPSC-CM迁移和/或成熟的底物形貌。
Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) raise many possibilities for cardiac research but they exhibit an immature phenotype, which influences experimental outcomes. The aim of our research is to investigate the effects of a topographical gradient substrate on the morphology and function of commercially available hiPSC-CM. The lateral dimensions the microgrooves on the substrate varied from 8 to 100 μm space between the 8 μm grooves on one axis and from ∼5 nm to ∼1 μm in depth on the other axis. Cells were seeded homogeneously across the substrate and according to the manufacturers protocols. At days 4 and 10, measures of eccentricity, elongation, orientation, sarcomere length (SL), and contractility of the hiPSC-CM were taken. Only the deepest and widest region (8–30 μm wide and 0.85–1 μm deep) showed a significantly higher percentage of hiPSC-CM with an increased eccentricity (31.3 ± 6.4%), elongation (10.4 ± 4.3%), and orientation (<10°) (32.1 ± 2.7%) when compared with the control (flat substrate) (15.8 ± 5.0%, 3.4 ± 2.7%, and 10.6 ± 1.1%, respectively). Additionally, during stimulus-induced contraction, the relaxation phase of the twitch was prolonged (400 ms) compared to nonelongated cells (200 ms). These findings support the potential use of dual microgradient substrates to investigate substrate topographies that stimulate migration and/or maturation of hiPSC-CM.
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DOI：
10.1073/pnas.1508073112
发表时间：
2015-10-13
影响因子：
11.1
作者：
Ribeiro, Alexandre J. S.;Ang, Yen-Sin;Pruitt, Beth L.
通讯作者：
Pruitt, Beth L.
影响因子：
14
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.
通讯作者：
Terracciano, Cesare M.
DOI：
10.1115/1.4027145
发表时间：
2014-05-01
影响因子：
1.7
作者：
Rodriguez, Marita L.;Graham, Brandon T.;Sniadecki, Nathan J.
通讯作者：
Sniadecki, Nathan J.
影响因子：
64.8
作者：
Shiba, Yuji;Fernandes, Sarah;Zhu, Wei-Zhong;Filice, Dominic;Muskheli, Veronica;Kim, Jonathan;Palpant, Nathan J.;Gantz, Jay;Moyes, Kara White;Reinecke, Hans;Van Biber, Benjamin;Dardas, Todd;Mignone, John L.;Izawa, Atsushi;Hanna, Ramy;Viswanathan, Mohan;Gold, Joseph D.;Kotlikoff, Michael I.;Sarvazyan, Narine;Kay, Matthew W.;Murry, Charles E.;Laflamme, Michael A.
通讯作者：
Laflamme, Michael A.
影响因子：
13.3
作者：
Reynolds, Paul M.;Pedersen, Rasmus H.;Gadegaard, Nikolaj
通讯作者：
Gadegaard, Nikolaj