Analysis of the mechanism underlying liver diseases using human induced pluripotent stem cells

Analysis of the mechanism underlying liver diseases using human induced pluripotent stem cells
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DOI:
10.1080/25785826.2019.1657254
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发表时间:
2019-04
影响因子:
4.4
通讯作者:
S. Kakinuma;Mamoru Watanabe
S. Kakinuma;Mamoru Watanabe
中科院分区:
--
文献类型:
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作者:
S. Kakinuma;Mamoru Watanabe

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摘要 最近的研究结果表明,使用人诱导多能干(iPS)细胞的疾病模型概括了遗传性肝病、病毒性肝炎和肝纤维化的病理生理学。与原代肝细胞和癌细胞系相比,利用人类iPS细胞作为肝脏疾病模型具有几个显着的优势,例如无限扩展的潜力以及与正常肝细胞的生物学特性相似。在这篇综述中,我们重点关注使用人类 iPS 细胞对肝脏疾病进行建模,并讨论了支持此类疾病模型实用性的实验证据,包括我们最近的研究中的实验证据。转基因或源自患者的人类 iPS 细胞可以模仿先天性肝病表型。人类 iPS 衍生的肝细胞可以被肝炎病毒感染。人 iPS 衍生的肝细胞和间充质的共培养部分模拟了肝纤维化的过程。人iPS细胞来源的肝细胞及其共培养系统将有助于遗传性和非遗传性肝病病理生理学研究的进展以及治疗肝病的新治疗策略的开发。
Abstract 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.