Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Pittsburgh Liver Research Center, Human Synthetic Liver Biology Core, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Organogenesis. 2023 Dec 31;19(1):2247576. doi: 10.1080/15476278.2023.2247576.
Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), the most common types of cholestatic liver disease (CLD), result in enterohepatic obstruction, bile acid accumulation, and hepatotoxicity. The mechanisms by which hepatocytes respond to and cope with CLD remain largely unexplored. This study includes the characterization of hepatocytes isolated from explanted livers of patients with PBC and PSC. We examined the expression of hepatocyte-specific genes, intracellular bile acid (BA) levels, and oxidative stress in primary-human-hepatocytes (PHHs) isolated from explanted livers of patients with PBC and PSC and compared them with control normal human hepatocytes. Our findings provide valuable initial insights into the hepatocellular response to cholestasis in CLD and help support the use of PHHs as an experimental tool for these diseases.
原发性胆汁性胆管炎(PBC)和原发性硬化性胆管炎(PSC)是最常见的胆汁淤积性肝病(CLD)类型,可导致肝胆阻塞、胆汁酸蓄积和肝毒性。肝细胞对 CLD 作出反应和应对的机制在很大程度上仍未得到探索。本研究包括对源自 PBC 和 PSC 患者肝移植肝脏分离的肝细胞进行的特征描述。我们检测了源自 PBC 和 PSC 患者肝移植肝脏分离的原代人肝细胞(PHH)中肝细胞特异性基因的表达、细胞内胆汁酸(BA)水平和氧化应激情况,并与正常供体来源的人肝细胞进行了比较。我们的研究结果为深入了解 CLD 中肝细胞对胆汁淤积的反应提供了有价值的初步见解,并支持将 PHH 作为这些疾病的实验工具使用。