Department of Developmental Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Department of Medicine, Gastroenterology Section, Center for Regenerative Medicine, Boston University and Boston Medical Center, Boston, Massachusetts.
Semin Liver Dis. 2023 Feb;43(1):13-23. doi: 10.1055/s-0042-1760306. Epub 2023 Feb 10.
The liver field has been debating for decades the contribution of the plasticity of the two epithelial compartments in the liver, hepatocytes and biliary epithelial cells (BECs), to derive each other as a repair mechanism. The hepatobiliary plasticity has been first observed in diseased human livers by the presence of biphenotypic cells expressing hepatocyte and BEC markers within bile ducts and regenerative nodules or budding from strings of proliferative BECs in septa. These observations are not surprising as hepatocytes and BECs derive from a common fetal progenitor, the hepatoblast, and, as such, they are expected to compensate for each other's loss in adults. To investigate the cell origin of regenerated cell compartments and associated molecular mechanisms, numerous murine and zebrafish models with ability to trace cell fates have been extensively developed. This short review summarizes the clinical and preclinical studies illustrating the hepatobiliary plasticity and its potential therapeutic application.
几十年来,肝脏领域一直在争论两个上皮隔室(肝细胞和胆管上皮细胞)的可塑性在作为修复机制互相衍生方面的贡献。肝内胆管细胞和肝细胞的可塑性首先在患病的人类肝脏中被观察到,表现为在胆管和再生结节内表达肝细胞和胆管上皮细胞标志物的双表型细胞,或者从隔室内增殖的胆管上皮细胞条索上芽生。这些观察结果并不奇怪,因为肝细胞和胆管上皮细胞来源于共同的胎肝祖细胞——肝前体细胞,因此,预计它们在成人中可以相互代偿。为了研究再生细胞隔室的细胞起源和相关分子机制,已经开发了许多具有追踪细胞命运能力的小鼠和斑马鱼模型。这篇简短的综述总结了说明肝胆可塑性及其潜在治疗应用的临床前和临床研究。