The analysis for proliferation and differentiation of hepatic stem cells

在这里，我们发现，持续性损伤诱导有效的转分化为功能性肝细胞的骨髓基质细胞。通过高静脉向四氯化碳诱导的肝硬化小鼠注射1 × 10^5个未经处理的绿色荧光蛋白（GFP）阳性BMC。在这些小鼠中，移植的GFP阳性BMCS在一天后有效地迁移到肝小叶的门静脉周围区域，并在4周时重新填充受体肝脏的四分之一。相反，移植到对照小鼠后未检测到GFP阳性的BMCs。没有受损的肝脏BMCs通过未成熟的成肝细胞转分化为功能性成熟肝细胞。血清白蛋白明显升高，以弥补慢性肝功能衰竭的BMC移植。这些结果表明，受体条件和微环境是使用BMC成功进行细胞治疗的关键因素。我们将该模型命名为GFP/CC 14模型。作为下一步，我们开发了一种新的单克隆抗体，抗Liv 8 usi ...更多信息 ng小鼠胎肝抗原。在胚胎第11.5天，Liv 8阳性细胞出现在野生型小鼠的肝脏中，但没有AML 1基因敲除小鼠的肝脏中，后者缺乏造血系统。Liv 8阳性细胞占成年小鼠BMC的32%，包括CD 45阳性细胞。我们利用自动磁性细胞分选系统分离Liv 8阳性或阴性细胞，然后将这些细胞移植到连续性肝损伤模型中。一周后，在Liv 8阳性和Liv 8阴性细胞的受体之间，BMC在肝脏中的初始定殖没有显著差异，但在4周时，用Liv 8阴性细胞观察到更有效的BMC转分化成肝细胞。目前，我们正试图鉴定抗Liv 8的抗原。这些分析将有助于开发所有有效的细胞治疗来修复受损的肝脏。另一方面，我们发现了这种新的蛋白质。人类Maid同源物（HHM）是一种螺旋-环-螺旋（HLH）转录调控蛋白，参与肝干细胞的发育和分化。我们分析了HHM在肝癌发生中的潜在参与。我们通过原位杂交和免疫组化分析，评估了HHM在大鼠肝癌发生的缺氯L-氨基酸限定（CDAA）饮食模型和人HCC样本中的表达。HHM在病灶和HCC中高表达。提示HHM可能是检测肝癌发生的一个有用的标志蛋白。

Here we found that persistent injury induced efficient trans-differentiation of BMCs into functional hepatocytes. Liver cirrhosis mice induced by carbon tetrachloride were injected with 1x10^5 non-treated green fluorescent protein (GFP)-positive BMCs via tall vein. In these mice, transplanted GFP-positive BMCS efficiently migrated into the peri-portal area of liver lobules after one day and repopulated one-fourth of the recipient liver by 4 weeks. In contrast, no GFP-positive BMCs were detected following transplantation into control mice. with undamaged livers. BMCs trans-differentiated into functional mature hepatocytes via immature hepatoblasts. Serum albumin was significantly elevated to compensate for chronic liver failure by BMC transplantation. These results showed that the recipient condition and microenvironments are key factors for successful cell therapy using BMC. We named this model as a GFP/CC14 model. As the next step, we developed a new monoclonal antibody, anti-Liv8 usi … More ng mouse fetal liver antigen. On embryonic day 11.5, Liv8-positive cells were seen in the liver of wild-tape, but not AML1 knockout mice, which lack the hematopoietic system. Liv8-positive cells accounted for 32% of the BMC in adult mice and included CD45-positive cells. We separated Liv8-positive or Liv8-negative cells using Auto Magnetic Cell Sorting system, and then transplanted these cells to a continuous liver damaged model. After one week, there was no marked difference in the initial colonization of BMC in the liver between recipients of Liv8-positive and Liv8-negative cells, but at 4 weeks more efficient BMC trans-differentiation into hepatocytes was seen with Liv8-negative cells. Now we are trying to identify the antigen of anti-Liv8. These analysis will be useful to develop all efficient cell therapy to repair damaged liver. On the other hands, we identified that new protein. Human homologue of maid (HHM) is a helix-loop-helix (HLH) transcriptional regulatory protein that is involved in the hepatic stem cell development and differentlation. We analyzed the potential involvement of HHM in hepatocarcinogenesis. We assessed HHM expression in the chorine deficient L-amino acid defined (CDAA) diet model of rat hepatocarcinogenesis by in situ hybridization DISH), and human HCC samples by immunohistochemical analysis. High HHM expression was seen in foci and HCC. These results suggested that HHM may be a useful marker protein to detect initiation of hepatocarcinogenesis Less