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

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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.