Hepatic progenitor cells in the mouse extrahepatic bile duct after a bile duct ligation
Hepatic progenitor cells in the mouse extrahepatic bile duct after a bile duct ligation
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DOI：
10.1089/scd.2007.0037
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发表时间：
2007-12-01
影响因子：
4
通讯作者：
Teraoka, Hirobumi
中科院分区：
文献类型：
--
作者：
Irie, Takumi;Asahina, Kinji;Teraoka, Hirobumi
在严重受损的肝脏中，肝内胆管被认为是肝祖细胞的来源。相比之下，肝祖细胞是否存在于肝外胆管(EHBD)的问题却鲜有人关注。在本研究中，我们检测了小鼠EHBD在胆管结扎后的表型变化。胆管结扎后，EHBD内c-Kit阳性的上皮细胞数量增加。结扎的EHBD表达c-Kit和Thy-1等肝祖细胞标志物的mRNA。胆管结扎后，肝细胞标志物如白蛋白和细胞色素P450 7al也在EHBD内瞬时检测到。在EHBD细胞培养中，我们检测到抗白蛋白抗体和白扁豆凝集素(一种胆管上皮细胞特异性凝集素)染色阳性的肝祖细胞。此外，在培养的EHBD群体中还发现了c-Kit和白蛋白阳性的肝祖细胞。此外，在培养中还观察到EHBD来源的肝细胞样细胞。一项移植研究显示，EHBD细胞整合到实质中，白蛋白阳性。这些数据表明，在胆管结扎后，EHBD中出现了肝祖细胞，随后形成了肝细胞样细胞。我们还观察到，胆管结扎后，胆汁中有肝细胞标志物的瞬时表达。我们的研究结果表明，EHBD和胆汁有可能成为治疗肝损伤的有用的可移植来源。
The intrahepatic bile duct has been suggested to be a source of hepatic progenitor cells in the severely damaged liver. In contrast, little attention has been paid to the question of whether hepatic progenitor cells exist in the extrahepatic bile duct (EHBD). In the present study, we examined the phenotypic changes of the mouse EHBD following bile duct ligation. After bile duct ligation, the number of c-Kit-positive epithelial cells increased in the EHBD. The ligated EHBD expressed mRNA for hepatic progenitor cell markers, including c-Kit and Thy-1. Hepatocyte markers such as albumin and cytochrome P450 7al were also transiently detected in the EHBD after a bile duct ligation. In a culture of EHBD cells, we detected hepatic progenitor cells that were positive for both staining with anti-albumin antibodies and Dolichos biflorus agglutinin, a biliary epithelial cell-specific lectin. Furthermore, hepatic progenitor cells positive for both c-Kit and albumin were found in the cultured EHBD population. Additionally EHBD-derived hepatocyte-like cells were also observed in the culture. A transplantation study revealed that EHBD cells integrate into the parenchyma and are albumin positive. These data suggest that hepatic progenitor cells emerge in the EHBD following bile duct ligation, that subsequently give rise to hepatocyte-like cells. We also observed that the gall bladder transiently expressed hepatocyte markers after bile duct ligation. Our results suggest a potential of the EHBD and gall bladder as useful transplantable sources for liver injury.