Kakinuma Sei, Watanabe Mamoru
Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University (TMDU) , Tokyo , Japan.
Department of Liver Disease Control, Tokyo Medical and Dental University (TMDU) , Tokyo , Japan.
Immunol Med. 2019 Jun;42(2):71-78. doi: 10.1080/25785826.2019.1657254. Epub 2019 Sep 9.
Results of recent studies have shown that disease models using human induced pluripotent stem (iPS) cells have recapitulated the pathophysiology of genetic liver diseases, viral hepatitis and hepatic fibrosis. The utilization of human iPS cells as a model of liver diseases has several substantial advantages compared with primary hepatocytes and cancer cell lines, such as the potential for unlimited expansion and similarity of biological characteristics to normal liver cells. In this review, we have focused on modeling liver diseases using human iPS cells and discussed the experimental evidence that supports the utility of such disease models, including that in our recent studies. Genetically modified or patient-derived human iPS cells can mimic congenital liver disease phenotypes. Human iPS-derived hepatic cells can be infected with the hepatitis viruses. The co-culture of human iPS-derived hepatocytes and mesenchyme partially mimics the process of liver fibrosis. Human iPS cell-derived hepatic cells and the co-culture system of such cells will contribute to the progress of studies on the pathophysiology of genetic and non-genetic liver diseases and development of novel therapeutic strategies for treating liver diseases.
近期研究结果表明，使用人诱导多能干细胞（iPS细胞）构建的疾病模型已再现了遗传性肝病、病毒性肝炎和肝纤维化的病理生理学过程。与原代肝细胞和癌细胞系相比，利用人iPS细胞作为肝病模型具有若干显著优势，如具有无限扩增的潜力以及生物学特性与正常肝细胞相似。在本综述中，我们重点关注了利用人iPS细胞构建肝病模型，并讨论了支持此类疾病模型实用性的实验证据，包括我们近期研究中的证据。基因编辑的或患者来源的人iPS细胞可模拟先天性肝病表型。人iPS细胞来源的肝细胞可被肝炎病毒感染。人iPS细胞来源的肝细胞与间充质的共培养可部分模拟肝纤维化过程。人iPS细胞来源的肝细胞及其共培养系统将有助于推动遗传性和非遗传性肝病病理生理学研究以及肝病新治疗策略的开发。
