Université de Nantes, Inserm, TENS, The Enteric Nervous System in Gut and Brain Diseases, IMAD, Nantes, France.
Université de Nantes, Inserm, TENS, The Enteric Nervous System in Gut and Brain Diseases, IMAD, Nantes, France; Department of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States; Department of Pediatrics, University of Cincinnati, Cincinnati, OH, United States.
Methods Cell Biol. 2020;159:175-199. doi: 10.1016/bs.mcb.2020.04.012. Epub 2020 May 27.
The use of human pluripotent stem cells (hPSCs) and differentiation techniques offer new ways to generate specific tissue. It is now possible to differentiate hPSC into human intestinal organoids that include an enteric nervous system. Using step-wise differentiation processes, we generate innervated intestinal organoids that form three-dimensional structures bearing an epithelium, neurons and glial cells embedded in a supporting mesenchyme. Innervated organoids further develop to a complex structure with similar organization and cellular differentiation as the developing intestine. These tools open up new fields of application in the study of the development and pathophysiology of enteric neuropathies. Herein, we describe the generation of both human intestinal organoids and vagal neural crest cells from hPSC and their combination into an innervated organoid. We also discuss technical considerations for these experiments, and highlight advantages and limitations of the system.
使用人类多能干细胞（hPSC）和分化技术为生成特定组织提供了新途径。现在可以将 hPSC 分化为包含肠神经系统的人类肠类器官。通过逐步分化过程，我们生成了具有神经支配的肠类器官，这些类器官形成具有上皮细胞、神经元和神经胶质细胞的三维结构，嵌入在支持性间质中。具有神经支配的类器官进一步发育成具有与发育中肠道相似的组织和细胞分化的复杂结构。这些工具为研究肠神经病变的发育和病理生理学开辟了新的应用领域。本文描述了从 hPSC 生成人类肠类器官和迷走神经嵴细胞，并将它们组合成具有神经支配的类器官。我们还讨论了这些实验的技术注意事项，并强调了该系统的优点和局限性。
