Shek Dmitrii, Chen Dishen, Read Scott A, Ahlenstiel Golo
Blacktown Clinical School, Western Sydney University, Blacktown, NSW, Australia; Storr Liver Centre, The Westmead Institute for Medical Research, University of Sydney, Westmead, NSW, Australia; Blacktown Hospital, Blacktown, NSW, Australia.
Storr Liver Centre, The Westmead Institute for Medical Research, University of Sydney, Westmead, NSW, Australia.
Cancer Lett. 2021 Jul 10;510:48-58. doi: 10.1016/j.canlet.2021.04.008. Epub 2021 Apr 20.
The World Health Organization predicts that by 2030 liver cancer will cause 1 million deaths annually, thus becoming the third most lethal cancer worldwide. Hepatocellular carcinoma and cholangiocarcinoma are the two major primary cancer subtypes involving the liver. Both are often diagnosed late, and hence response to treatment and survival are poor. It is therefore of utmost importance to understand the mechanisms by which liver cancers initiate and progress. The causes of primary liver cancer are diverse, resulting primarily from obesity, chronic alcohol abuse or viral hepatitis. Importantly, both alcohol and high fat diet can promote intestinal permeability, enabling microbial translocation from the gut into the liver. As a result, these microbial antigens and metabolites exacerbate hepatic inflammation and fibrosis, increasing the risk of primary liver cancer. Organoids are primary, three-dimensional, stem cell derived liver models that can recapitulate many of the disease phenotypes observed in vivo. This review aims to summarize the advantages of organoid culture to examine the gut-liver axis with respect to cancer initiation and progression. In particular, the use of gut and liver organoid mono- and co-cultures together and with immune cell populations to best recapitulate disease mechanisms and develop therapeutic interventions.
世界卫生组织预测，到2030年，肝癌每年将导致100万人死亡，从而成为全球第三大致命癌症。肝细胞癌和胆管癌是涉及肝脏的两种主要原发性癌症亚型。这两种癌症通常在晚期才被诊断出来，因此对治疗的反应和生存率都很差。因此，了解肝癌发生和发展的机制至关重要。原发性肝癌的病因多种多样，主要源于肥胖、长期酗酒或病毒性肝炎。重要的是，酒精和高脂肪饮食都会增加肠道通透性，使微生物从肠道转移到肝脏。因此，这些微生物抗原和代谢产物会加剧肝脏炎症和纤维化，增加原发性肝癌的风险。类器官是源自原代、三维干细胞的肝脏模型，能够重现许多在体内观察到的疾病表型。本综述旨在总结类器官培养在研究肠道-肝脏轴与癌症发生和发展方面的优势。特别是，将肠道和肝脏类器官单培养和共培养，以及与免疫细胞群体一起使用，以最好地重现疾病机制并开发治疗干预措施。
