Basic research for the production of human hepatocytes and the transplantation of hepatic tissues

本研究旨在建立大量制备小肝细胞、肝祖细胞的方法，并建立肝类器官的体外形成方法。此外，我们研究了如何将细胞和组织移植到肝脏中。与成熟肝细胞不同，SHs的生长受Follistatin/Activin系统的调控。卵圆细胞即肝干细胞虽经SHs分化为肝细胞，但不能完全成熟。移植的肝干/祖细胞不能在受体肝脏中长期存活，并因细胞衰老而消失。因此，肝干/祖细胞在严重肝功能衰竭中的作用可能是短暂地补偿肝功能的丧失。通过构建大鼠肝窦、星状细胞和内皮细胞模型，阐明了静止的星状细胞可能调控内皮细胞的毛细血管形成和肝窦的成熟。

We aimed to develop the methods of producing a large number of small hepatocytes(SHs), hepatic progenitor cells, and to establish the methods of hepatic organoid formation in vitro. In addition, we examined how cells and tissues could be transplanted into liver. Unlike mature hepatocytes the growth of rat SHs was regulated by Follistatin/Activin system. Although oval cells, hepatic stem cells, differentiated into hepatocytes via SHs, they could not completely mature. The transplanted hepatic stem/progenitor cells could not survive for a long term in the recipient liver and disappeared by cellular senescence. Thus, the role of hepatic stem/progenitor cells in severe liver failure may be to compensate for the lost hepatic functions transiently. To use the model of hepatic sinusoids constituting rat SHs, stellate cells, and endothelial cells, we clarified that quiescent stellate cells might regulate the capillary formation of endothelial cells and maturation of SHs.