美国辛辛那提儿童医院医疗中心James M. Wells研究团队发现，从多能干细胞中分别提取的三个初级胚层可以设计出功能性的人类胃肠器官。2021年12月1日，国际知名学术期刊《细胞—干细胞》在线发表了这一成果。

研究人员开发了一种类器官组装方法，从三个初级胚层的细胞开始——肠道神经胶质、间质和上皮前体，它们分别来自人类多能干细胞（PSC）。从这三种类型的细胞中，研究人员生成了人类的胃窦和胃底组织，其中含有分化的腺体，周围是含有功能性肠道神经元的平滑肌层，控制着工程化的胃窦组织收缩。

利用这个实验系统，研究人员表明人类的肠神经嵴细胞（ENCC）促进了间质的发育和前胃类器官腺体的形态发生。此外，ENCC可以直接作用于前肠，促进后部命运，从而形成具有布鲁纳腺表型的器官。因此，从PSC中单独提取的生殖层成分可用于组织工程，从而生成复杂的人类器官。

据了解，人类类器官模型系统缺乏重要的细胞类型，这些细胞将在胚胎发育过程中被整合入器官组织。

附：英文原文

Title: Functional human gastrointestinal organoids can be engineered from three primary germ layers derived separately from pluripotent stem cells

Author: Alexandra K. Eicher, Daniel O. Kechele, Nambirajan Sundaram, H. Matthew Berns, Holly M. Poling, Lauren E. Haines, J. Guillermo Sanchez, Keishi Kishimoto, Mansa Krishnamurthy, Lu Han, Aaron M. Zorn, Michael A. Helmrath, James M. Wells

Issue&Volume: 2021-12-01

Abstract: Human organoid model systems lack important cell types that, in the embryo, are incorporatedinto organ tissues during development. We developed an organoid assembly approachstarting with cells from the three primary germ layers—enteric neuroglial, mesenchymal,and epithelial precursors—that were derived separately from human pluripotent stemcells (PSCs). From these three cell types, we generated human antral and fundic gastrictissue containing differentiated glands surrounded by layers of smooth muscle containingfunctional enteric neurons that controlled contractions of the engineered antral tissue.Using this experimental system, we show that human enteric neural crest cells (ENCCs)promote mesenchyme development and glandular morphogenesis of antral stomach organoids.Moreover, ENCCs can act directly on the foregut to promote a posterior fate, resultingin organoids with a Brunner’s gland phenotype. Thus, germ layer components that arederived separately from PSCs can be used for tissue engineering to generate complexhuman organoids.

DOI: 10.1016/j.stem.2021.10.010

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(21)00435-5