Immunolocalization of OV-6, a putative progenitor cell marker in human fetal and diseased pediatric liver
Immunolocalization of OV-6, a putative progenitor cell marker in human fetal and diseased pediatric liver
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DOI：
10.1002/hep.510280412
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发表时间：
1998-10-01
期刊：
影响因子：
13.5
通讯作者：
Strain, AJ
中科院分区：
文献类型：
--
作者：
Crosby, HA;Hubscher, SG;Strain, AJ
人类肝脏中是否存在祖细胞（干细胞）仍然存在争议。在肝癌发生和损伤的啮齿动物模型中，卵圆细胞在汇管束的门静脉周围区域增殖，并且被认为源自干细胞区室，因为它们能够分化为肝细胞或胆管上皮细胞。在这项研究中，大鼠卵圆细胞标记物 OV-6 被用来研究胎儿和儿童肝脏中存在干细胞的假设。将 OV-6 的表达模式与已建立的成人胆管细胞标志物人上皮抗原 125 (HEA-125) 和细胞角蛋白 19 (CK-19) 进行比较。在正常儿科肝脏 (n = 7) 中，胆管和胆管用 CK-19 和 HEA-125 进行免疫染色，而 OV-6 染色始终呈阴性。在胎儿组织 (n = 10) 中，导管板细胞、原始胆管和成肝细胞均被 CK-19 和 HEA-125 染色，尽管只有部分导管板细胞和成肝细胞呈 OV-6 阳性。在胆道闭锁 (n = 6) 和 alpha 1、抗胰蛋白酶缺乏症 (alpha 1,AT) (n = 4) 中，CK-19 和 HEA-125 免疫染色的导管增殖细胞倾向于形成精细的吻合导管，而 OV-6 染色更多地发现于局限于汇管边缘的离散细胞。此外，在患病肝脏中，OV-6 在肝细胞小叶中呈强阳性，在间隔周区域强度最高。这种广泛的肝细胞 OV-6 阳性表明该抗体可以识别已取代成熟细胞的分化程度较低的表型细胞（移行肝细胞）。因此，有人提出，在人肝脏中，OV-6正在识别具有祖干细胞样表型的细胞，这些细胞具有分化为OV-6阳性导管细胞或小叶肝细胞的能力。
The existence of progenitor (stem) cells in the human liver remains a matter of debate. In rodent models of hepatocarcinogenesis and injury, oval cells proliferate in the periportal regions of the portal tracts and are suggested to derive from a stem cell compartment, because they are capable of differentiating into hepatocytes or biliary epithelial cells. In this study, the rat oval cell marker, OV-6 has been used to investigate the hypothesis that there are stem cells present in fetal and pediatric human liver. The pattern of OV-6 expression was compared with the established adult biliary cell markers human epithelial antigen-125 (HEA-125) and cytokeratin-19 (CK-19). In normal pediatric liver (n = 7), bile ducts and ductules were immunostained with CK-19 and HEA-125, whereas OV-6 staining was consistently negative. In fetal tissue (n = 10), ductal plate cells, primitive bile ducts, and hepatoblasts were stained with CK-19 and HEA-125 although only some of the ductal plate cells and hepatoblasts were OV-6 positive. In biliary atresia (n = 6) and alpha 1, anti-trypsin deficiency (alpha 1,AT) (n = 4), CK-19 and HEA-125 immunostained ductular proliferative cells that tended to form finely anastomosing ductules, whereas OV-6 staining was found more on discrete cells confined to portal tract margins. Additionally, in diseased liver, OV-6 was strongly positive in hepatocyte lobules with greatest intensity in the periseptal regions. This widespread hepatocyte OV-6 positivity suggests that the antibody may identify cells of a less differentiated phenotype (transitional hepatocytes) that have replaced the mature cells. Therefore, it is proposed that in human liver, OV-6 is recognizing cells with a progenitor stem cell-like phenotype with the capacity to differentiate into OV-6 positive ductular cells or lobular hepatocytes.