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从前肠中肠边界对人类肝胆胰腺器官产生模型

Hiroyuki Koike^1,2, Kentaro Iwasawa^1,2, Rie Ouchi^1,2

¹Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.

|September 27, 2019

概括

研究人员使用人类多能干细胞开发了一种新的3D培养模型来研究人类内皮器官生成. 这种模型成功地回顾了肝脏,胆汁和胰腺器官结构的整合.

科学领域:

发育生物学
干细胞生物学
机体生成

背景情况:

器官生成涉及邻近组织之间的复杂相互作用.
了解这些组件如何协调形成多器官结构仍然是一个挑战.

研究的目的:

从人类多能干细胞中研究肝脏,胆道和胰腺结构的连续模式和动态形态发生.
建立一个新的体外模型来研究人类内皮器官生成.

主要方法:

使用人类多能干细胞的3D培养来产生前后肠球体.
研究了球体之间的边界相互作用,以诱导视网膜酸依赖器官域的出现.
对多器官发育和形态遗传事件进行了长期培养的微解剖器官的分析.

主要成果:

从人类多能干细胞成功生成了肝脏,胆汁和胰腺器官集成域.
在前肠-中肠边界表现出依赖于视网膜酸的器官域.
在3D器官模型中观察到早期形态遗传事件的回顾,包括发育和分支.
展示了HES1中的基因突变破坏了胆道特异性,反映了体内观察.

结论:

在3D培养系统中对前肠和中肠组织进行并置,可以建立实验性的多器官综合模型.
该模型为研究复杂的人体内皮质器官生成和相关发育障碍提供了一个可操作和可访问的平台.

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