Department of Anatomical, Histological, Forensic Medicine and Orthopedic Sciences, University of Rome "Sapienza", Rome, Italy; ; Eleonora Lorillard Spencer-Cenci Foundation, Rome, Italy;
Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy;
Hepatobiliary Surg Nutr. 2013 Apr;2(2):68-77. doi: 10.3978/j.issn.2304-3881.2012.10.11.
Hepatic stem/progenitor cells (HPCs) are stem cells residing in the most peripheral branches of the biliary tree; these cells are able to differentiate towards mature hepatocyte or mature cholangiocyte; moreover in normal conditions, they are mostly quiescent cells. HPC activation has been involved in the progression of chronic parenchymal diseases (chronic viral hepatitis) and chronic biliary diseases (such as Primary Biliary Cirrhosis: PBC) and in the occurrence of intrahepatic cholangiocarcinoma. The HPCs participate in the repair of liver damage either through the replacement of dead cells or by driving fundamental repair processes, including fibrosis and angiogenesis. Little information exists regarding the expression of VEGF by HPC in the course of liver non-malignant pathologies. In this study, we evaluated: (I) the presence of HPCs in PBC and HCV-related Cirrhosis (HCV-C) samples, and (II) the expression of VEGFs and VEGF-Rs in PBC and HCV-C samples. Our results showed (I) PBC samples presented a more extensive expansion of HPC population in comparison with those of HCV-C samples; (II) PBC samples showed a more extensive angiogenesis if compared to HCV-C; and (III) PBC samples were characterized by an increased expression of VEGF-A and VEGF-C if compared to HCV-C and the number of HPCs expressing VEGFs was correlated with the extension of ductular reaction and angiogenesis. The role of VEGFs in the expansion of HPC niche could have important implication in the management of fibrogenic processes and carcinogenesis.
肝干细胞/祖细胞 (HPCs) 是位于胆道树最外周分支的干细胞；这些细胞能够向成熟肝细胞或成熟胆管细胞分化；此外，在正常情况下，它们大多是静止细胞。HPC 的激活已涉及慢性实质疾病（慢性病毒性肝炎）和慢性胆道疾病（如原发性胆汁性肝硬化：PBC）的进展以及肝内胆管癌的发生。HPC 通过替代死亡细胞或通过驱动包括纤维化和血管生成在内的基本修复过程参与肝损伤的修复。关于 HPC 在非恶性肝病理过程中表达 VEGF 的信息很少。在这项研究中，我们评估了：(I) PBC 和 HCV 相关肝硬化 (HCV-C) 样本中 HPC 的存在，以及 (II) PBC 和 HCV-C 样本中 VEGFs 和 VEGF-Rs 的表达。我们的结果表明：(I) PBC 样本中 HPC 群体的扩张比 HCV-C 样本更为广泛；(II) 与 HCV-C 相比，PBC 样本表现出更广泛的血管生成；(III) 与 HCV-C 相比，PBC 样本中 VEGF-A 和 VEGF-C 的表达增加，并且表达 VEGFs 的 HPC 数量与胆管反应和血管生成的扩展相关。VEGFs 在 HPC 龛位扩张中的作用可能对纤维发生过程和癌变的管理具有重要意义。
