Development of liver regeneration therapy against severe hepatic failure based on stem cell science -Differentiation and growth of hepatic stem cell and cell transplantation.

我们正在尝试开发一种创新的治疗严重肝功能衰竭的方法，即移植肝干细胞。在此治疗中，分离表达Musashi-1基因的肝干细胞是重要的一步。2003年，我们在大鼠肝损伤模型中发现肝干细胞的一个细胞系卵圆细胞表达Musashi-1基因。Musashi-1基因在卵形细胞中的表达受notch和jagged -1信号转导通路的调控。2004年，我们利用Matrigel开发了骨髓细胞向肝细胞表型分化的培养系统。骨髓细胞表达肝细胞特异性基因，如白蛋白、甲胎蛋白、细胞角蛋白8和色氨酸2,3-二氧酶。此外，Matrigel上的细胞呈肝索样结构。本研究发现：1)存在可分化为肝细胞表型的骨髓细胞，2)移植的骨髓细胞在肝损伤严重时可锚定在肝内，3)骨髓细胞在Matrigel上可有效生长并分化为肝细胞。

We are trying to develop an innovative therapy for severer hepatic failure to transplant hepatic stem cells. In this therapy, It is an important step to isolate hepatic stem cells expressing Musashi-1 gene.In 2003 we showed that oval cells, a cell lineage of hepatic stem cells, expressed Musashi-1 gene in rat liver injury model. The expression of Musashi-1 gene in oval cells was regulated by signal transduction pathways through notch and jagged 1.In 2004, we development of culture system using Matrigel, in which bone marrow cells could differentiated into phenotype of hepatocytes. Bone marrow cells expressed hepatocyte-specific genes such as albumin, AFP, cytokeratin 8, and tryptophan-2,3-dioxygenease. Further, the cells on Matrigel showed hepatic cord-like structure.This study demonstrated findings as follows : 1)there exist bone marrow cell which can differentiate into hepatocyte-phenotype, 2)transplanted bone marrow cells could anchor in the liver when the liver injury was severe, 3)bpne marrow cell could effectively grow and differentiate into hepatocytes on Matrigel.