Sirica A E
Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0297, USA.
Histol Histopathol. 1995 Apr;10(2):433-56.
Ductular hepatocytes are observed in the livers of both experimental animals and man under various conditions of severe toxin-, carcinogen- or viral-induced hepatic injury with prominent loss of parenchymal hepatocytes. These unique hepatic epithelial cells are characterized by phenotypic traits that are intermediate between those of hepatocytes and intrahepatic biliary epithelium. The origin of ductular hepatocytes is controversial, but it has been hypothesized that they may represent a transitional cell stage associated with either (1) a ductular metaplasia of parenchymal hepatocytes into intrahepatic biliary epithelium, (2) a metaplastic conversion of intrahepatic bile duct or ductular epithelium into hepatocytes, or (3) differentiation of a putative liver stem cell along the hepatocyte lineage. Depending on the liver disease state being investigated, evidence is presented to support all three of these possibilities. Of particular interest is the increasing evidence supporting the existence of a facultative pluripotent stem-like cell associated with the intrahepatic biliary tract, which appears capable of differentiating into various gut endoderm-derived cell types, including hepatocytes, small intestinal mucosal cells, and pancreatic acinar cells. Ductular cells of pancreas have also been demonstrated to alter their differentiation commitment under various induced conditions of pancreatic injury and regeneration, so as to give rise to pancreatic hepatocytes. The presence of a putative stem-like cell in liver together with the plasticity exhibited by some hepatocytes and biliary epithelial cells in various forms of severe hepatic and biliary tract injury can have important implications for carcinogenesis and aberrant regenerative responses in liver. In addition, novel in vivo and cell culture models have been developed, which are serving as potentially powerful tools for investigating the effects of specific growth factors, extracellular matrix components, hormones and other agents on the ability of nonparenchymal epithelial liver cell types to differentiate into hepatocyte-like cells.
在实验动物和人类肝脏中，在各种严重毒素、致癌物或病毒诱导的肝损伤且实质肝细胞大量丧失的情况下，均可观察到小胆管肝细胞。这些独特的肝上皮细胞具有介于肝细胞和肝内胆管上皮细胞之间的表型特征。小胆管肝细胞的起源存在争议，但据推测，它们可能代表一个过渡细胞阶段，与以下任一情况相关：(1) 实质肝细胞向肝内胆管上皮的小胆管化生；(2) 肝内胆管或小胆管上皮向肝细胞的化生转变；或(3) 假定的肝干细胞沿肝细胞谱系分化。根据所研究的肝脏疾病状态，有证据支持所有这三种可能性。特别令人感兴趣的是，越来越多的证据支持存在一种与肝内胆管相关的兼性多能干细胞样细胞，它似乎能够分化为各种肠道内胚层来源的细胞类型，包括肝细胞、小肠黏膜细胞和胰腺腺泡细胞。胰腺的小导管细胞也已被证明在胰腺损伤和再生的各种诱导条件下会改变其分化方向，从而产生胰腺肝细胞。肝脏中假定的干细胞样细胞的存在，以及一些肝细胞和胆管上皮细胞在各种严重肝和胆管损伤形式中表现出的可塑性，可能对肝脏的致癌作用和异常再生反应具有重要意义。此外，已经开发出新型的体内和细胞培养模型，它们正作为潜在的强大工具，用于研究特定生长因子、细胞外基质成分、激素和其他因素对非实质肝上皮细胞类型分化为肝细胞样细胞能力的影响。
