Development of strategic therapy for severe hepatic failure using regenerative medicine-Isolation of hepatic stem cell expressing musashi-1 gene and cell therapy

肝干细胞移植是治疗严重肝功能衰竭的一种新方法。2001年，我们从大鼠肝脏中建立了一个卵圆细胞系，即双能干细胞系。该细胞系同时表达musashi-1基因和AFP、CK-18基因。随着细胞系通过球体形成而分化，Musashi-1基因表达被抑制。此外，7个人肝癌细胞系中有3个表达musashi-1基因。2002年我们发现musashi-1基因通过抑制Numb基因的表达来调节Notch信号通路。此外，musashi-1基因在肝脏发育中的作用正在使用基因敲除小鼠进行研究。

We are trying to develop an innovative therapy for sever hepatic failure to transplant hepatic stem cell. In this therapy, it is an important step to isolate hepatic stem cell expressing musashi-1 gene.In 2001 we established a cell line of oval cells, bipotent stem cells, from rat livers. This cell line expressed musashi-1 gene with AFP and CK-18 ones. With differenciation of the cell line by spheroid formation, the musashi-1 gene expression was suppressed. Moreover, three of seven human hepatoma cell lines expressed musashi-1 gene. This implied that musashi-1 gene might participate in differentiation of hepatic stem cells and hepatic carcinogenesis.In 2002, we found that the musashi-1 gene regulated notch signalin via suppression of Numb gene expression. Also, role of musashi-1 gene in liver development is under investigation using knockout mice of the gene.