Vessey C J, de la Hall P M
Department of Anatomical Pathology, University of Cape Town, South Africa.
Pathology. 2001 May;33(2):130-41.
The existence of a liver stem cell population has only gained credence recently, following the results of animal experiments. These cells are thought to reside in the terminal bile ductules (canals of Hering). Hepatocyte division is responsible for liver regeneration after most causes of injury. However, stem cells may contribute to hepatocyte regeneration, or even take over this role if the liver injury is severe and associated with an impairment of hepatocyte proliferation as in cirrhosis or submassive/massive necrosis, due to drugs, toxins or viruses. "Oval" cells are the descendants of the stem cells and are found in the portal and periportal regions in experimental animals within days of the liver injury. These cells proliferate to form narrow ductules, which may stain positively for biliary cytokeratins CK 19, and radiate out into the damaged parenchyma. Both in vitro and in vivo animal studies now suggest that oval cells can differentiate into bile ductular cells or hepatocytes to allow repopulation of the injured liver. As the oval cells differentiate into hepatocytes they may show positive staining for pyruvate kinase isoenzyme L-PK, albumin and alpha-fetoprotein. There is also growing evidence that bone marrow stem cells may contribute to liver regeneration. The possible involvement of hepatic stem cells in the development of dysplastic nodules, hepatocellular carcinoma and cholangiocarcinoma has been suggested but remains highly controversial. Oval cell isolation and culture techniques, together with stem cell transplantation strategies, may in the future provide novel treatments for individuals with inherited and acquired hepatic disorders.
直到最近动物实验取得成果后，肝干细胞群的存在才获得认可。这些细胞被认为存在于终末胆小管（赫林管）中。大多数损伤原因导致肝脏损伤后，肝细胞分裂负责肝脏再生。然而，干细胞可能有助于肝细胞再生，或者在肝脏损伤严重且伴有肝细胞增殖受损（如肝硬化或亚大块/大块坏死，由药物、毒素或病毒引起）时，甚至接管这一作用。“卵圆”细胞是干细胞的后代，在肝损伤数天内可在实验动物的门静脉和门周区域发现。这些细胞增殖形成狭窄的胆小管，其可能对胆管细胞角蛋白CK 19呈阳性染色，并向受损实质放射状延伸。现在体外和体内动物研究均表明，卵圆细胞可分化为胆管细胞或肝细胞，以使受损肝脏重新细胞化。当卵圆细胞分化为肝细胞时，它们可能对丙酮酸激酶同工酶L-PK、白蛋白和甲胎蛋白呈阳性染色。也有越来越多的证据表明骨髓干细胞可能有助于肝脏再生。肝干细胞可能参与发育异常结节、肝细胞癌和胆管癌的发生，这一点已被提出，但仍极具争议。卵圆细胞分离和培养技术，以及干细胞移植策略，未来可能为患有遗传性和获得性肝脏疾病的个体提供新的治疗方法。
