人肝脏疾病和肝细胞癌中的干细胞鉴定。
The identification of stem cells in human liver diseases and hepatocellular carcinoma.
机构信息
Department of Pathology, Harbor-UCLA Medical Center, Torrance, CA 90509, USA.
出版信息
Exp Mol Pathol. 2010 Jun;88(3):331-40. doi: 10.1016/j.yexmp.2010.01.003. Epub 2010 Jan 18.
UNLABELLED
Liver stem cells are thought to preside in bile ducts and the canals of Hering. They extend into the liver parenchyma at a time when normal liver cell proliferation is suppressed and liver regeneration is stimulated. In the present study 69 liver biopsies and surgically excised liver tumors were studied for the presence of liver stem cells. It was found that human cirrhotic livers and hepatocellular carcinomas (HCC) frequently exhibited isolated single scattered hepatocyte stem cells within the liver parenchyma rather than in the portal tract, bile duct or the canal of Hering. These cells expressed liver stem cell markers. HCCs also contained isolated tumor cell which expressed the same stem cell markers. The markers used were GST-P, OV-6, CK-19, Oct-3/4 and FAT10. They were identified by immunofluorescent antibody staining. HGF, EGF, CK19, AIR, H19, Nanog, Oct-3/4 and FAT10 were identified by RNA-FISH. H19 is a non-coding RNA, which is expressed in most HCCs.
RESULTS
Immunohistochemistry and RNA-FISH performed on human livers identified isolated stem cells in liver parenchyma as follows: Stem cells identified by immunohistochemical markers (OV-6 and GST-P) and RNA-FISH markers (HGF, EGF, CK19 and H19) were found scattered in the liver parenchyma of cirrhotic livers and within hepatocellular carcinomas (HCCs). Precirrhotic ASH or NASH all stained negative for these stem cells. In HCCs, 13 out of 15 had stem cells located within the tumor (78%). In cirrhotic livers, 12 out of 28 (37%) had liver parenchymal stem cells present. In one case of stage 3 precirrhosis, stem cells were also found. Double staining for the markers showed colocalization of the markers in stem cells. Stem cells were found in 33% of HBV, 47% of HCV, 25% of alcoholic steatohepatitis (ASH) and 17% of non-alcoholic steatohepatitis (NASH). The frequency of stem cells found in the different disease categories correlates with the frequency of HCC occurring in these different diseases.
未加标签
肝干细胞被认为存在于胆管和 Hering 管中。当正常肝细胞增殖受到抑制而肝再生受到刺激时，它们会延伸到肝实质中。在本研究中，对 69 份肝活检和手术切除的肝肿瘤进行了肝干细胞存在情况的研究。结果发现，人类肝硬化和肝细胞癌（HCC）常在内脏实质中发现孤立的单个散在的肝细胞干细胞，而不是在门脉区、胆管或 Hering 管中。这些细胞表达肝干细胞标志物。HCC 还包含表达相同干细胞标志物的孤立肿瘤细胞。所用的标志物是 GST-P、OV-6、CK-19、Oct-3/4 和 FAT10。它们通过免疫荧光抗体染色进行鉴定。HGF、EGF、CK19、AIR、H19、Nanog、Oct-3/4 和 FAT10 通过 RNA-FISH 进行鉴定。H19 是一种非编码 RNA，在大多数 HCC 中表达。
结果
对人类肝脏进行免疫组化和 RNA-FISH 检测，确定了肝实质中孤立的干细胞如下：通过免疫组织化学标记物（OV-6 和 GST-P）和 RNA-FISH 标记物（HGF、EGF、CK19 和 H19）鉴定的干细胞散在肝硬化肝脏和肝细胞癌（HCC）的肝实质中。前驱性 ASH 或 NASH 均未为这些干细胞染色。在 HCC 中，15 例中有 13 例（78%）位于肿瘤内的干细胞。在肝硬化肝脏中，28 例中有 12 例（37%）存在肝实质干细胞。在一例 3 期前驱性肝硬化中，也发现了干细胞。标记物的双重染色显示标记物在干细胞中存在共定位。在 33%的乙型肝炎病毒、47%的丙型肝炎病毒、25%的酒精性脂肪性肝炎（ASH）和 17%的非酒精性脂肪性肝炎（NASH）中发现了干细胞。在不同疾病类别中发现的干细胞的频率与这些不同疾病中发生 HCC 的频率相关。
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