Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, Via Borelli 50, 00161 Rome, Italy.
Department of Movement, Human and Health Sciences, Division of Health Sciences, University of Rome "Foro Italico", Piazza Lauro de Bosis 6, 00135 Rome, Italy.
Int J Mol Sci. 2018 Sep 25;19(10):2917. doi: 10.3390/ijms19102917.
Two distinct stem/progenitor cell populations of biliary origin have been identified in the adult liver and biliary tree. Hepatic Stem/progenitor Cells (HpSCs) are bipotent progenitor cells located within the canals of Hering and can be differentiated into mature hepatocytes and cholangiocytes; Biliary Tree Stem/progenitor Cells (BTSCs) are multipotent stem cells located within the peribiliary glands of large intrahepatic and extrahepatic bile ducts and able to differentiate into hepatic and pancreatic lineages. HpSCs and BTSCs are endowed in a specialized niche constituted by supporting cells and extracellular matrix compounds. The actual contribution of these stem cell niches to liver and biliary tree homeostatic regeneration is marginal; this is due to the high replicative capabilities and plasticity of mature parenchymal cells (i.e., hepatocytes and cholangiocytes). However, the study of human liver and biliary diseases disclosed how these stem cell niches are involved in the regenerative response after extensive and/or chronic injuries, with the activation of specific signaling pathways. The present review summarizes the contribution of stem/progenitor cell niches in human liver diseases, underlining mechanisms of activation and clinical implications, including fibrogenesis and disease progression.
已在成体肝脏和胆道中鉴定出两种不同的胆管源性干/祖细胞群体。肝干细胞/祖细胞（HpSCs）是位于 Hering 管内的双能祖细胞，可分化为成熟的肝细胞和胆管细胞；胆管树干细胞/祖细胞（BTSCs）是位于大肝内和肝外胆管周围的胆管腺内的多能干细胞，能够分化为肝和胰腺谱系。HpSCs 和 BTSCs 存在于由支持细胞和细胞外基质化合物组成的特定生态位中。这些干细胞生态位对肝脏和胆道的稳态再生的实际贡献是微不足道的；这是由于成熟实质细胞（即肝细胞和胆管细胞）具有高复制能力和可塑性。然而，对人类肝脏和胆道疾病的研究揭示了这些干细胞生态位如何在广泛和/或慢性损伤后参与再生反应，激活特定的信号通路。本综述总结了干细胞/祖细胞生态位在人类肝脏疾病中的作用，强调了激活机制和临床意义，包括纤维化和疾病进展。
