Biowire: a platform for maturation of human pluripotent stem cell-derived cardiomyocytes.
Biowire: a platform for maturation of human pluripotent stem cell-derived cardiomyocytes.
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DOI：
10.1038/nmeth.2524
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发表时间：
2013-08
期刊：
影响因子：
48
通讯作者：
Radisic, Milica
中科院分区：
文献类型：
--
作者：
Nunes, Sara S.;Miklas, Jason W.;Liu, Jie;Aschar-Sobbi, Roozbeh;Xiao, Yun;Zhang, Boyang;Jiang, Jiahua;Masse, Stephane;Gagliardi, Mark;Hsieh, Anne;Thavandiran, Nimalan;Laflamme, Michael A.;Nanthakumar, Kumaraswamy;Gross, Gil J.;Backx, Peter H.;Keller, Gordon;Radisic, Milica
定向分化方案能够从人多能干细胞 (hPSC) 中衍生出心肌细胞，并允许在体外对人心肌进行工程改造。然而，hPSC 衍生的心肌细胞反映了非常早期的人类发育，限制了它们在生成成熟心肌的体外模型中的效用。在这里，我们开发了一个新平台，将微型系统中的三维细胞培养与电刺激相结合，以成熟 hPSC 衍生的心脏组织。我们利用定量结构、分子和电生理学分析来阐明未成熟的人类心肌对电刺激和起搏的反应。我们证明了该工程平台可以生成具有频繁条纹的 3 维对齐心脏组织（生物线）。与未刺激的对照组相比，接受电刺激的生物线显着增加了肌原纤维的超微结构组织，表现出较高的传导速度，并改变了电生理学和 Ca2+ 处理特性。这些变化与心肌细胞成熟一致，并且取决于刺激率。
Directed differentiation protocols enable derivation of cardiomyocytes from human pluripotent stem cells (hPSC) and permit engineering of human myocardium in vitro. However, hPSC-derived cardiomyocytes are reflective of very early human development, limiting their utility in the generation of in vitro models of mature myocardium. Here, we developed a new platform that combines three-dimensional cell cultivation in a microfabricated system with electrical stimulation to mature hPSC-derived cardiac tissues. We utilized quantitative structural, molecular and electrophysiological analyses to elucidate the responses of immature human myocardium to electrical stimulation and pacing. We demonstrated that the engineered platform allowed for the generation of 3-dimensional, aligned cardiac tissues (biowires) with frequent striations. Biowires submitted to electrical stimulation markedly increased myofibril ultrastructural organization, displayed elevated conduction velocity and altered both the electrophysiological and Ca2+ handling properties versus non-stimulated controls. These changes were in agreement with cardiomyocyte maturation and were dependent on the stimulation rate.
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影响因子：
5
作者：
McDevitt, TC;Laflamme, MA;Murry, CE
通讯作者：
Murry, CE
影响因子：
4.8
作者：
Chattergoon, Natasha N.;Giraud, George D.;Thornburg, Kent L.
通讯作者：
Thornburg, Kent L.
DOI：
10.1016/j.pbiomolbio.2012.07.012
发表时间：
2012-10
影响因子：
3.8
作者：
Blazeski A;Zhu R;Hunter DW;Weinberg SH;Boheler KR;Zambidis ET;Tung L
通讯作者：
Tung L
影响因子：
64.8
作者：
Laflamme, Michael A.;Murry, Charles E.
通讯作者：
Murry, Charles E.
DOI：
10.1073/pnas.0407817101
发表时间：
2004-12-28
影响因子：
11.1
作者：
Radisic, M;Park, H;Vunjak-Novakovic, G
通讯作者：
Vunjak-Novakovic, G