Improvement of Hepatic Functions by Spheroid Formation and Culture with Fibroblasts in 3D Silica Nonwoven Fabrics

Improvement of Hepatic Functions by Spheroid Formation and Culture with Fibroblasts in 3D Silica Nonwoven Fabrics
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3D 二氧化硅无纺布中成纤维细胞的球体形成和培养改善肝功能

DOI:
10.1166/jnn.2019.16103
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发表时间:
2019
期刊:
J. Nanosci. Nanotechnol.
影响因子:
--
通讯作者:
and Hidenori Otsuka
and Hidenori Otsuka
中科院分区:
--
文献类型:
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作者:
Shohei Ishikawa;Kazutoshi Iijima;Kohei Sasaki;Masaaki Kawabe;and Hidenori Otsuka

文献摘要

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为了实现芯片上器官作为再生医学和药物开发的有效工具,人们开发了长期促进肝脏特异性功能的组织模拟细胞培养方法。我们先前已经证明,利用微图案化的底物在成纤维细胞上共培养肝细胞球体可以改善肝功能,这是由于细胞与细胞之间的异型相互作用和彼此之间的旁分泌信号。此外,单层培养的肝细胞功能在与成纤维细胞单层培养的单独共培养中也得到了促进,且在3D二氧化硅非织造布中与成纤维细胞单独共培养的效果更好。在这项研究中,分别将肝细胞球体与3D二氧化硅非织造布上的成纤维细胞共培养,以进一步改善肝细胞功能。与成纤维细胞共培养比单一球体培养更能促进肝功能的恢复。在3D二氧化硅非织造布中,单独与成纤维细胞共培养时,功能增强效果最明显。因此,这些结果表明,成纤维细胞在3D二氧化硅非织造布上的3D培养增加了旁分泌因子的异型分泌,这对改善肝功能是必要的。
In order to realize organ-on-a-chip as an effective tool for regenerative medicine and drug development, tissue-mimic cell culture methods which promote liver-specific function for long period have been developed. We have previously demonstrated that coculture of hepatocyte spheroids on fibroblasts using micropatterned substrate improved the hepatic functions due to the heterotypic cell–cell interactions and paracrine signaling from each other. In addition, hepatocyte function cultured as monolayer was also promoted in separately coculture with fibroblasts cultured as monolayer, and it is more improved in separately coculture with fibroblasts in 3D silica nonwoven fabrics. In this study, separately coculture of hepatocyte spheroids with fibroblasts cultured on 3D silica nonwoven fabrics was estimated for further improvement of hepatocyte functions. The hepatic function cocultured with fibroblast was more promoted than mono spheroids culture. The functional enhancement was significantly most improved in separately coculture with fibroblast in 3D silica nonwoven fabrics. Thus, these results were suggested that 3D culture of fibroblasts in 3D silica nonwoven fabrics increased the heterotypic secretion of paracrine factors, and it is essential for improved hepatic performance.