Bioinspired onion epithelium-like structure promotes the maturation of cardiomyocytes derived from human pluripotent stem cells†,Biomaterials Science

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Bioinspired onion epithelium-like structure promotes the maturation of cardiomyocytes derived from human pluripotent stem cells†
Biomaterials Science ( IF 5.8 ) Pub Date : 2017-06-12 00:00:00 , DOI: 10.1039/c7bm00132k
Cong Xu _{1,

2,

3,

4,

5} , Li Wang _{1,

2,

3,

4,

5} , Yue Yu _{1,

2,

3,

4,

5} , Fangchao Yin _{1,

2,

3,

4,

5} , Xiaoqing Zhang _{1,

2,

3,

4,

5} , Lei Jiang _{1,

2,

3,

4,

5} , Jianhua Qin _{1,

2,

3,

4,

5}

Affiliation

Organized cardiomyocyte alignment is critical to maintain the mechanical properties of the heart. In this study, we present a new and simple strategy to fabricate a biomimetic microchip designed with an onion epithelium-like structure and investigate the guided behavior of human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) on the substrate. The hiPSC-CMs were observed to be confined by the three dimensional surficial features morphologically, analogous to the in vivo microenvironment, and exhibited an organized anisotropic alignment on the onion epithelium-like structure with good beating function. The calcium imaging of hiPSC-CMs demonstrated a more mature Ca²⁺ spark pattern as well. Furthermore, the expression of sarcomere genes (TNNI3, MYH6 and MYH7), potassium channel genes (KCNE1 and KCNH2), and calcium channel genes (RYR2) was significantly up-regulated on the substrate with an onion epithelium-like structure instead of the surface without the structure, indicating a more matured status of cardiomyocytes induced by this structure. It appears that the biomimetic micropatterned structure, analogous to in vivo cellular organization, is an important factor that might promote the maturation of hiPSC-CMs, providing new biological insights to guide hiPSC-CM maturation by biophysical factors. The established approach may offer an effective in vitro model for investigating cardiomyocyte differentiation, maturation and tissue engineering applications.

中文翻译：

受生物启发的洋葱上皮样结构促进源自人多能干细胞的心肌细胞的成熟†

有组织的心肌细胞排列对于维持心脏的机械特性至关重要。在这项研究中，我们提出了一种新的简单策略来制造具有洋葱上皮样结构的仿生微芯片，并研究了人类诱导的多能干细胞衍生的心肌细胞（hiPSC-CMs）在基质上的指导行为。观察到hiPSC-CMs受形态上的三维表面特征限制，类似于体内的微环境，并且在洋葱上皮样结构上表现出有序的各向异性排列，具有良好的搏动功能。hiPSC-CMs的钙成像显示更成熟的Ca ²⁺火花图案也是如此。此外，在具有洋葱上皮样结构而不是表面的底物上，肌节基因（TNNI3，MYH6和MYH7），钾通道基因（KCNE1和KCNH2）和钙通道基因（RYR2）的表达显着上调。如果没有该结构，则表明由该结构诱导的心肌细胞处于更成熟的状态。看来，类似于体内细胞组织的仿生微图案结构是可能促进hiPSC-CM成熟的重要因素，提供了新的生物学见解，以通过生物物理因素指导hiPSC-CM的成熟。既定的方法可能会提供有效的体外方法 用于研究心肌细胞分化，成熟和组织工程应用的模型。

更新日期：2017-06-12

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