Hoshiba Takashi, Otaki Takayuki, Nemoto Eri, Maruyama Hiroka, Tanaka Masaru
†Graduate School of Science and Engineering, Yamagata University, 4-3-16 Jonan, Yonezawa, Yamagata 992-8510, Japan.
‡International Center for Materials Nanoarchitectonics, National Institute for Materials Science, 1-1 Namiki, Tsukuba, Ibaraki 305-0044, Japan.
ACS Appl Mater Interfaces. 2015 Aug 19;7(32):18096-103. doi: 10.1021/acsami.5b05210. Epub 2015 Aug 10.
The development of bioartificial liver (BAL) is expected because of the shortage of donor liver for transplantation. The substrates for BAL require the following criteria: (a) blood compatibility, (b) hepatocyte adhesiveness, and (c) the ability to maintain hepatocyte-specific functions. Here, we examined blood-compatible poly(2-methoxyethyl acrylate) (PMEA) and poly(tetrahydrofurfuryl acrylate) (PTHFA) (PTHFA) as the substrates for BAL. HepG2, a human hepatocyte model, could adhere on PMEA and PTHFA substrates. The spreading of HepG2 cells was suppressed on PMEA substrates because integrin contribution to cell adhesion on PMEA substrate was low and integrin signaling was not sufficiently activated. Hepatocyte-specific gene expression in HepG2 cells increased on PMEA substrate, whereas the expression decreased on PTHFA substrates due to the nuclear localization of Yes-associated protein (YAP). These results indicate that blood-compatible PMEA is suitable for BAL substrate. Also, PMEA is expected to be used to regulate cell functions for blood-contacting tissue engineering.
由于用于移植的供体肝脏短缺，生物人工肝（BAL）的发展备受期待。BAL的底物需要满足以下标准：（a）血液相容性，（b）肝细胞粘附性，以及（c）维持肝细胞特异性功能的能力。在此，我们研究了具有血液相容性的聚（丙烯酸2-甲氧基乙酯）（PMEA）和聚（丙烯酸四氢糠酯）（PTHFA）作为BAL的底物。人肝细胞模型HepG2能够粘附在PMEA和PTHFA底物上。HepG2细胞在PMEA底物上的铺展受到抑制，因为整合素对PMEA底物上细胞粘附的贡献较低，且整合素信号未被充分激活。HepG2细胞中肝细胞特异性基因表达在PMEA底物上增加，而在PTHFA底物上由于Yes相关蛋白（YAP）的核定位而降低。这些结果表明，具有血液相容性的PMEA适用于BAL底物。此外，PMEA有望用于调节与血液接触的组织工程中的细胞功能。
