Analysis of the serum factor which promotes the repopulation and differentiation of the bone marrow cell into hepatocyte.

我们建立了GFP/CC14模型来评估骨髓细胞向肝细胞的分化。我们发现骨髓细胞（BMC）在受损肝脏中重新填充并分化为产生白蛋白的肝细胞，在这种情况下，BMC输注也显著改善了肝纤维化，提高了存活率。基于这些结果，我们开始了临床研究：自体BMC输注治疗肝硬化患者（干细胞，2006）。在此，我们通过蛋白质组学分析来寻找促进BMC向肝细胞再生和分化的血清因子。BMC输注后血清载脂蛋白明显升高。我们还分析了哪些生长因子调控BMC的再生和分化。我们发现FGF2是BMC向肝细胞再生和分化的重要生长因子。另一方面，我们也探讨了肝干细胞分化的机制。在此之前，我们还克隆了Maid作为肝干细胞分化调节因子的人类同源物。在本研究中，我们开始制作Maid KO小鼠，分析Maid如何调节BMC向肝细胞的分化。

We developed the GFP/CC14 model to evaluate the differentiation of bone marrow cell into hepatocyte. We found that bone marrow cell (BMC) were repopulated into the damaged liver and differentiated into albumin-producing hepatocyte In this condition, liver fibrosis was also significantly improved and survival rate was improved by BMC infusion. Depend on these results, we started the clinical study : Autologous BMC infusion therapy for liver cirrhosis patients (Stem Cells 2006). Here we did the proteomics analysis to find serum factor that promote repopulation and differentiation of BMC into hepatocyte. Apolipoprotein was increased significantly in the serum after BMC infusion. We also analyzed which growth factors regulate the repopulation and differentiation of BMC. We found that FGF2 was important growth factor to repopulate and differentiation of BMC into hepatocyte. On the other hands, we also examine the mechanism of the differentiation of liver stem cell. Previously we also cloned Human Homologue of Maid as a regulator of differentiation of hepatic stem cell. In this study, we started to make the Maid KO mouse to analyze how Maid regulate the differentiation of BMC into hepatocyte.