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将库弗弗细胞集成到人类iPSC衍生的肝脏器官中,用于模拟毒性肝脏功能障碍的模型

Yang Li¹, Yunzhong Nie², Xia Yang¹

¹Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Minato, Tokyo 108-8639, Japan; Division of Regenerative Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Minato, Tokyo 108-8639, Japan.

|March 7, 2024

概括

研究人员用库弗弗细胞 (KuLOs) 开发了人类肝脏器官 (LO),用于模拟败血症. 这些KuLOs模仿败血性肝功能障碍并显示恢复,为研究肝炎提供了一个新的工具.

科学领域:

干细胞生物学干细胞生物学
免疫学免疫学免疫学
肝病学肝病学是一种肝病学.

背景情况:

人类肝脏器官 (LO) 对于模拟肝脏疾病至关重要.
整合天生的免疫细胞,如库弗弗细胞,对于精确的败血性肝脏建模至关重要.
目前的模型缺乏居住性巨细胞,这限制了它们在研究败血症方面的实用性.

研究的目的:

开发一种产生含有库弗弗细胞 (KuLO) 的人类肝脏器官的策略.
研究这些KuLOs在模拟人类败血性肝脏病理生理学的潜力.
探索治疗性干预的败血症诱导的肝功能障碍使用这个模型.

主要方法:

用人诱导的多能干干细胞 (hiPSC) 衍生的红骨髓状原始体 (EMP) 和 hiPSC 衍生的 LOs 来总结胎儿肝血形成.
补充巨细胞殖民地刺激因子 (M-CSF) 以维持血液形成群体.
暴露KuLOs与败血症类内毒素,并评估器官功能障碍.
使用托尔类受体-4导向内毒素抗剂评估功能恢复.

主要成果:

通过回顾胎儿肝脏血液生成,成功生成含有库弗弗细胞 (KuLOs) 的肝脏器官.
证明LOs促进EMP血液形成向髓状和红状腺血统.
暴露于内毒素的KuLOs表现出显著的功能障碍,反映了人类败血性肝病理.
在内毒素消除后观察到KuLOs显著的功能恢复,由TLR4抗剂加速.

结论:

开发了一个全面的框架,用于将造血细胞集成到肝脏器官中.
库洛作为一个强大的模型来研究由炎症介导的肝脏病理,特别是败血症.
这种模型有助于深入研究败血性肝损伤的治疗策略.

关键词:

科普:干细胞研究这是一个EMP EMP EMP.库弗弗细胞是库弗弗细胞.在 TLR4 中,疾病模型的疾病模型.血液形成血液形成人类的iPSCs.肝脏的炎症肝脏的炎症肝脏有机体是肝脏的有机体.自己恢复的自我恢复.这是一种血症.

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