Alison M R, Golding M H, Sarraf C E
Department of Histopathology, Royal Postgraduate Medical School, London, UK.
Cell Prolif. 1996 Jul;29(7):373-402. doi: 10.1111/j.1365-2184.1996.tb00982.x.
The ability of the liver to regenerate after parenchymal damage is usually accomplished by the ephemeral entry of normally proliferatively quiescent (G0) hepatocytes into the cell cycle. However, when hepatocyte regeneration is defective, arborizing ductules which are continuous with the biliary tree, proliferate and migrate into the surrounding parenchyma. In man these biliary cells have variously been referred to as ductular structures, neoductules and neocholangioles, and have been observed in many forms of chronic liver disease, including cancer. In experimental animals similar ductal cells are usually called oval cells, and their association with defective regeneration has led to the belief that these cells represent a progenitor cell population. Oval cells are thought to take over the burden of regenerative growth after substantial hepatocyte loss, suggesting that they are the progeny of facultative stem cells. The liver is not, however, generally considered as a stem cell-fed hierarchy, although this is disputed by others. Despite this, the subject of oval cells has aroused intense interest as these cells may represent a target population for hepatic carcinogens, and they may be useful vehicles for ex vivo gene therapy. This review proposes that the liver does harbour stem cells which are located throughout the biliary epithelium, and that oval cells represent the progeny of these stem cells and function as an amplification compartment for the generation of 'new' hepatocytes. This is a conditional process which only occurs when the regenerative capacity of hepatocytes is overwhelmed and thus, unlike the intestinal epithelium, the liver is not behaving as a classical continually renewing stem cell-fed lineage. We focus on the biliary network, not merely as a conduit for bile, but also as a cell compartment with the potential to proliferate under appropriate conditions and give rise to fully differentiated hepatocytes and other cell types.
肝实质损伤后肝脏的再生能力通常是通过正常处于增殖静止期（G0期）的肝细胞短暂进入细胞周期来实现的。然而，当肝细胞再生存在缺陷时，与胆管树相连的树枝状小胆管会增殖并迁移到周围实质中。在人类，这些胆管细胞有多种称谓，如导管结构、新生小胆管和新生胆小管，在包括癌症在内的多种慢性肝病中均有观察到。在实验动物中，类似的导管细胞通常被称为卵圆细胞，它们与再生缺陷的关联使人们认为这些细胞代表了祖细胞群体。卵圆细胞被认为在大量肝细胞丢失后承担起再生生长的重任，这表明它们是兼性干细胞的后代。然而，肝脏一般不被视为由干细胞驱动的层级结构，尽管其他人对此存在争议。尽管如此，卵圆细胞这一主题引发了强烈的兴趣，因为这些细胞可能是肝致癌物的靶细胞群体，并且它们可能是体外基因治疗的有用载体。本综述提出，肝脏确实含有位于整个胆管上皮的干细胞，卵圆细胞代表这些干细胞的后代，并作为产生“新”肝细胞的扩增区室发挥作用。这是一个有条件的过程，仅在肝细胞的再生能力不堪重负时才会发生，因此，与肠上皮不同，肝脏并非作为经典的持续更新的由干细胞驱动的谱系发挥作用。我们关注胆管网络，不仅因为它是胆汁的通道，还因为它是一个细胞区室，在适当条件下有增殖潜力，并能产生完全分化的肝细胞和其他细胞类型。
