Graduate School of Sciences, Tokyo University of Science, 1-3 Kagurazaka, Shinjuku-ku, Tokyo 162-8601, Japan.
Department of Industrial Chemistry, Faculty of Engineering, Tokyo University of Science, 12-1 Ichigayafunagawara-machi, Shinjuku-ku, Tokyo 162-0826, Japan.
J Nanosci Nanotechnol. 2019 Jun 1;19(6):3326-3333. doi: 10.1166/jnn.2019.16103.
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.
为了实现器官芯片作为再生医学和药物开发的有效工具，已经开发出了促进长期肝脏特异性功能的组织模拟细胞培养方法。我们之前已经证明，使用微图案化基质将肝球体与成纤维细胞共培养可以改善肝脏功能，这是由于异质细胞-细胞相互作用和来自彼此的旁分泌信号。此外，单层培养的成纤维细胞也可以促进单层培养的肝细胞功能，而与 3D 硅非织造织物中的成纤维细胞共培养则进一步改善了肝细胞功能。在这项研究中，评估了与在 3D 硅非织造织物上培养的成纤维细胞分别共培养的肝球体，以进一步改善肝细胞功能。与成纤维细胞共培养的肝功能比单球体培养更能促进。与 3D 硅非织造织物中的成纤维细胞分别共培养时，功能增强最为显著。因此，这些结果表明，3D 硅非织造织物中成纤维细胞的 3D 培养增加了旁分泌因子的异质分泌，这对于改善肝脏性能是必不可少的。
