Integrated in vit-roin vivo organization of liver tissues having a functional bile duct network

为了组织具有功能性胆管网络的可植入肝组织，首先，我们制备了由胎鼠肝细胞和从大鼠分离的成熟胆管上皮细胞构成的球形细胞聚集体。在整个聚集体上具有连续和功能性胆管网络的聚集体成功地形成在含有比胎肝细胞大三倍的成熟胆管细胞的聚集体中。当这样的聚集体被固定在聚-L-乳酸支架与基质胶，并被植入到免疫缺陷小鼠的肠系膜，胆管网络得到很好的保持在具有成熟的胆管细胞的聚集体的情况下，而它们没有形成在纯胎肝细胞聚集体的情况下。这些结果表明，成熟的胆管细胞是必要的，在组织的肝组织形成功能性胆管网络。

To organize implantable liver tissues having a functional bile duct network, first, we made spherical cellular aggregates constituted of fetal rat liver cells and mature bile duct epithelial cells isolated from rats. Aggregates having a continuous and functional bile duct network over the entire aggregates were successfully formed in the aggregates containing a three times larger number of mature bile duct cells over fetal liver cells. When such aggregates were immobilized in poly-L-lactic acid scaffolds with Matrigel and were implanted into the mesentery of immune-deficient mice, bile duct networks were well maintained in the case of aggregates having mature bile duct cells, whereas they were not formed in the case of pure fetal liver cell aggregates. These results showed that mature bile duct cells are necessary in forming functional bile duct networks over organized liver tissues.