Silicon nanowire-induced maturation of cardiomyocytes derived from human induced pluripotent stem cells.

Silicon nanowire-induced maturation of cardiomyocytes derived from human induced pluripotent stem cells.
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DOI:
10.1021/nl502227a
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发表时间:
2015-05-13
期刊:
影响因子:
10.8
通讯作者:
Mei Y
Mei Y
中科院分区:
材料科学1区
文献类型:
--
作者:
Tan Y;Richards D;Xu R;Stewart-Clark S;Mani SK;Borg TK;Menick DR;Tian B;Mei Y

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目前无法从人类多能干细胞中获得成熟的心肌细胞,这是将这种强大的技术转化为临床治疗的限制性步骤。为了解决这一问题,基于支架的组织工程方法已被用于体外模拟心脏发育并促进源自人多能干细胞的心肌细胞的成熟。虽然支架可以提供3D微环境,但目前的支架缺乏与天然细胞外环境相匹配的物理/化学/生物学特性。另一方面,无支架的3D心脏球体(即,通过将心肌细胞接种到琼脂糖微孔中制备的球形微组织)显示出改善心脏功能。然而,球状体内的心肌细胞不能以受控的方式组装,并导致受损的、不同步的收缩。在这里,我们第一次表明,掺入微量(即,~ 0.004%w/v)的导电硅纳米线(e-SiNW)可以形成导电网络,导致同步和显著增强的收缩(即,平均收缩幅度增加>55%),导致显著更先进的细胞结构和收缩成熟。
The current inability to derive mature cardiomyocytes from human pluripotent stem cells has been the limiting step for transitioning this powerful technology into clinical therapies. To address this, scaffold-based tissue engineering approaches have been utilized to mimic heart development in vitro and promote maturation of cardiomyocytes derived from human pluripotent stem cells. While scaffolds can provide 3D microenvironments, current scaffolds lack the matched physical/chemical/biological properties of native extracellular environments. On the other hand, scaffold-free, 3D cardiac spheroids (i.e., spherical-shaped microtissues) prepared by seeding cardiomyocytes into agarose microwells were shown to improve cardiac functions. However, cardiomyocytes within the spheroids could not assemble in a controlled manner and led to compromised, unsynchronized contractions. Here we show, for the first time, that incorporation of a trace amount (i.e., ~0.004% w/v) of electrically conductive silicon nanowires (e-SiNWs) in otherwise scaffold-free cardiac spheroids can form an electrically conductive network, leading to synchronized and significantly enhanced contraction (i.e., >55% increase in average contraction amplitude), resulting in significantly more advanced cellular structural and contractile maturation.
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