Sell S
Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, NY, USA.
Hepatology. 2001 Mar;33(3):738-50. doi: 10.1053/jhep.2001.21900.
It is hypothesized that the liver has 3 levels of cells in the hepatic lineage that respond to injury or carcinogenesis: 1) the mature hepatocyte, which responds to partial hepatectomy (PH), to centrolobular injury, such as that induced by carbon tetrachloride (CCl(4)), and to dimethylnitrosamine (DEN) hepatocarcinogenesis; 2) the ductular "bipolar" progenitor cell, which responds to centrolobular injury when the proliferation of hepatocytes is inhibited, and to N-2-acetylaminofluorene (AAF) hepatocarcinogenesis; and 3) the putative periductular stem cell, which responds to periportal injury, such as induced by allyl alcohol and to choline-deficiency models of hepatocarcinogenesis. Hepatocytes are numerous, respond rapidly by 1 or 2 cell cycles, but can only produce other hepatocytes. The ductular progenitor cells are less numerous, may proliferate for longer times than hepatocytes, and are generally considered "bipolar," i.e., can give rise to biliary cells or hepatocytes. Periductular stem cells are rare in the liver, have a very long proliferation potential, and may be multipotent, but their full potential has yet to be defined. Extrahepatic (bone marrow) origin of the periductular stem cells is supported by recent data showing that hepatocytes may express genetic markers of donor hematopoietic cells after bone marrow transplantation. Thus, experimental models of liver injury and of hepatocarcinogenesis may call forth a cellular response at different levels in the hepatic lineage (heterogeneity), and these cells have different potential to form cells of other types (plasticity).
据推测，肝脏肝谱系中有3种细胞水平对损伤或致癌作用作出反应：1）成熟肝细胞，对部分肝切除术（PH）、对小叶中心损伤（如四氯化碳（CCl₄）诱导的损伤）以及对二甲基亚硝胺（DEN）致癌作用作出反应；2）导管“双极”祖细胞，在肝细胞增殖受抑制时对小叶中心损伤作出反应，以及对N - 2 - 乙酰氨基芴（AAF）致癌作用作出反应；3）假定的导管周围干细胞，对门静脉周围损伤（如烯丙醇诱导的损伤）以及对致癌作用的胆碱缺乏模型作出反应。肝细胞数量众多，通过1或2个细胞周期迅速作出反应，但只能产生其他肝细胞。导管祖细胞数量较少，可能比肝细胞增殖更长时间，并且通常被认为是“双极的”，即可以产生胆管细胞或肝细胞。导管周围干细胞在肝脏中很少见，具有很长的增殖潜能，可能是多能的，但它们的全部潜能尚未确定。最近的数据支持导管周围干细胞的肝外（骨髓）起源，这些数据表明骨髓移植后肝细胞可能表达供体造血细胞的遗传标记。因此，肝损伤和肝癌发生的实验模型可能会在肝谱系的不同水平引发细胞反应（异质性），并且这些细胞具有形成其他类型细胞的不同潜能（可塑性）。
