Simulated Microgravity and 3D Culture Enhance Induction, Viability, Proliferation and Differentiation of Cardiac Progenitors from Human Pluripotent Stem Cells.
Simulated Microgravity and 3D Culture Enhance Induction, Viability, Proliferation and Differentiation of Cardiac Progenitors from Human Pluripotent Stem Cells.
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DOI：
10.1038/srep30956
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发表时间：
2016-08-05
影响因子：
4.6
通讯作者：
Xu C
中科院分区：
文献类型：
--
作者：
Jha R;Wu Q;Singh M;Preininger MK;Han P;Ding G;Cho HC;Jo H;Maher KO;Wagner MB;Xu C
从人多能干细胞高效产生心肌细胞对于其再生应用至关重要。微重力和3D培养可以深刻地调节细胞增殖和存活。在这里，我们从人类多能干细胞中设计了微型祖细胞心脏球体，并在其分化为心肌细胞期间使用随机定位机将球体暴露于模拟微重力下3天。该过程导致产生具有高活力（90%）和预期功能特性的高度富集的心肌细胞（99%纯度），与3D标准重力培养相比，来自每个未分化干细胞的心肌细胞的产率高1.5至4倍。在模拟微重力下的三维培养中观察到心脏祖细胞的诱导、增殖和活力增加以及与分化早期的增殖和存活相关的基因的上调。因此，3D培养和模拟微重力的组合可用于有效地产生高度富集的心肌细胞。
Efficient generation of cardiomyocytes from human pluripotent stem cells is critical for their regenerative applications. Microgravity and 3D culture can profoundly modulate cell proliferation and survival. Here, we engineered microscale progenitor cardiac spheres from human pluripotent stem cells and exposed the spheres to simulated microgravity using a random positioning machine for 3 days during their differentiation to cardiomyocytes. This process resulted in the production of highly enriched cardiomyocytes (99% purity) with high viability (90%) and expected functional properties, with a 1.5 to 4-fold higher yield of cardiomyocytes from each undifferentiated stem cell as compared with 3D-standard gravity culture. Increased induction, proliferation and viability of cardiac progenitors as well as up-regulation of genes associated with proliferation and survival at the early stage of differentiation were observed in the 3D culture under simulated microgravity. Therefore, a combination of 3D culture and simulated microgravity can be used to efficiently generate highly enriched cardiomyocytes.