球体
肝细胞
肝星状细胞
细胞生物学
旁分泌信号
化学
白蛋白
细胞培养
肝细胞学
细胞
生物物理学
生物
体外
生物化学
内分泌学
肝脏代谢
受体
遗传学
作者
Seung A. Lee,Da Yoon No,Edward Kang,Jongil Ju,Dong‐Sik Kim,Sang‐Hoon Lee
出处
期刊:Lab on a Chip
[The Royal Society of Chemistry]
日期:2013-01-01
卷期号:13 (18): 3529-3529
被引量:264
摘要
We have developed a three-dimensional (3D) liver-on-a-chip to investigate the interaction of hepatocytes and hepatic stellate cells (HSCs) in which primary 3D hepatocyte spheroids and HSCs are co-cultured without direct cell–cell contact. Here, we show that the 3D liver chip offers substantial advantages for the formation and harvesting of spheroids. The most important feature of this liver chip is that it enables continuous flow of medium to the cells through osmotic pumping, and thus requires only minimal handling and no external power source. We also demonstrate that flow assists the formation and long-term maintenance of spheroids. Additionally, we quantitatively and qualitatively investigated the paracrine effects of HSCs, demonstrating that HSCs assist in the maintenance of hepatocyte spheroids and play an important role in the formation of tight cell–cell contacts, thereby improving liver-specific function. Spheroids derived from co-cultures exhibited improved albumin and urea secretion rates compared to mono-cultured spheroids after 9 days. Immunostaining for cytochrome P450 revealed that the enzymatic activity of spheroids co-cultured for 8 days was greater than that of mono-cultured spheroids. These results indicate that this system has the potential for further development as a unique model for studying cellular interactions or as a tool that can be incorporated into other models aimed at creating hepatic structure and prolonging hepatocyte function in culture.
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