Cell number per spheroid and electrical conductivity of nanowires influence the function of silicon nanowired human cardiac spheroids.
Cell number per spheroid and electrical conductivity of nanowires influence the function of silicon nanowired human cardiac spheroids.
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DOI：
10.1016/j.actbio.2017.01.029
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发表时间：
2017-03-15
影响因子：
9.7
通讯作者：
Mei Y
中科院分区：
文献类型：
--
作者：
Tan Y;Richards D;Coyle RC;Yao J;Xu R;Gou W;Wang H;Menick DR;Tian B;Mei Y
人类诱导多能干细胞衍生的心肌细胞 (hiPSC-CM) 为治疗心血管疾病提供了无限的细胞来源，心血管疾病是全球死亡的主要原因。然而，目前的 hiPSC-CM 保留了不成熟的表型，导致移植后与成人心肌整合困难。为了解决这个问题，我们最近利用导电硅纳米线（e-SiNW）来促进 hiPSC-CM 的自组装，形成纳米线 hiPSC 心脏球体。我们之前的结果表明，e-SiNW 的添加有效增强了心脏球体的功能，并改善了 hiPSC-CM 的细胞成熟。在这里，我们研究了可能影响纳米线 hiPSC 心脏球体功能的两个重要因素：(1) 每个球体的细胞数量（即球体的大小），以及 (2) e-SiNW 的电导率。为了检查第一个因素，我们通过改变每个球体的细胞数量（∼0.5k、∼1k、∼3k、∼7k 细胞/球体）制备了四种不同尺寸的 hiPSC 心脏球体。研究发现，每个球体含有 ∼3k 个细胞的球体可以最大限度地发挥 3D 球体微环境的有益效果。这一结果用半定量理论来解释，该理论考虑了两个相互竞争的因素：1）3D 细胞间粘附力的改善，2）随着细胞数量的增加，球体中心的氧气供应减少。此外，硅纳米线的导电性在改善 hiPSC 心脏球体的组织功能方面的关键作用已得到证实。这些结果为开发合适的纳米线 hiPSC 心脏球体作为治疗心血管疾病的创新细胞输送系统奠定了坚实的基础。心血管疾病是全世界死亡和残疾的主要原因。由于成人心脏的再生能力有限，人类诱导多能干细胞来源的心肌细胞（hiPSC-CM）受到了极大的关注，因为它们为患者提供了特定的细胞来源来再生受损的心脏。尽管取得了进展，但目前的人类 hiPSC-CM 仍保留不成熟的表型，导致移植后与成人心肌整合困难。为了解决这个问题，我们最近利用导电硅纳米线（e-SiNW）来促进 hiPSC-CM 的自组装，形成纳米线 hiPSC 心脏球体。我们之前的结果表明，e-SiNW 的添加有效增强了心脏球体的功能，并改善了 hiPSC-CM 的细胞成熟。在这份手稿中，我们研究了两个重要因素对纳米线 hiPSC 心脏球体功能的影响：（1）每个球体的细胞数量（即球体的大小），以及（2）e-SiNW 的电导率。这些研究的结果将有助于开发合适的纳米线 hiPSC 心脏球体，以有效地递送 hiPSC-CM 进行心脏修复。
Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) provide an unlimited cell source to treat cardiovascular diseases, the leading cause of death worldwide. However, current hiPSC-CMs retain an immature phenotype that leads to difficulties for integration with adult myocardium after transplantation. To address this, we recently utilized electrically conductive silicon nanowires (e-SiNWs) to facilitate self-assembly of hiPSC-CMs to form nanowired hiPSC cardiac spheroids. Our previous results showed addition of e-SiNWs effectively enhanced the functions of the cardiac spheroids and improved the cellular maturation of hiPSC-CMs. Here, we examined two important factors that can affect functions of the nanowired hiPSC cardiac spheroids: (1) cell number per spheroid (i.e., size of the spheroids), and (2) the electrical conductivity of the e-SiNWs. To examine the first factor, we prepared hiPSC cardiac spheroids with four different sizes by varying cell number per spheroid (∼0.5k, ∼1k, ∼3k, ∼7k cells/spheroid). Spheroids with ∼3k cells/spheroid was found to maximize the beneficial effects of the 3D spheroid microenvironment. This result was explained with a semiquantitative theory that considers two competing factors: 1) the improved 3D cell-cell adhesion, and 2) the reduced oxygen supply to the center of spheroids with the increase of cell number. Also, the critical role of electrical conductivity of silicon nanowires has been confirmed in improving tissue function of hiPSC cardiac spheroids. These results lay down a solid foundation to develop suitable nanowired hiPSC cardiac spheroids as an innovative cell delivery system to treat cardiovascular diseases. Cardiovascular disease is the leading cause of death and disability worldwide. Due to the limited regenerative capacity of adult human hearts, human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have received significant attention because they provide a patient specific cell source to regenerate damaged hearts. Despite the progress, current human hiPSC-CMs retain an immature phenotype that leads to difficulties for integration with adult myocardium after transplantation. To address this, we recently utilized electrically conductive silicon nanowires (e-SiNWs) to facilitate self-assembly of hiPSC-CMs to form nanowired hiPSC cardiac spheroids. Our previous results showed addition of e-SiNWs effectively enhanced the functions of the cardiac spheroids and improved the cellular maturation of hiPSC-CMs. In this manuscript, we examined the effects of two important factors on the functions of nanowired hiPSC cardiac spheroids: (1) cell number per spheroid (i.e., size of the spheroids), and (2) the electrical conductivity of the e-SiNWs. The results from these studies will allow for the development of suitable nanowired hiPSC cardiac spheroids to effectively deliver hiPSC-CMs for heart repair.