Aix-Marseille University, CNRS, INSERM, Institut Paoli-Calmettes, CRCM, Epithelial Stem Cells and Cancer Team, CEDEX 09, 13273 Marseille, France.
Cincinnati Children's Hospital Medical Center, Department of Pediatric General and Thoracic Surgery, Cincinnati, OH 45229, USA.
Cells. 2021 May 27;10(6):1331. doi: 10.3390/cells10061331.
The gastrointestinal tract is a continuous series of organs from the mouth to the esophagus, stomach, intestine and anus that allows digestion to occur. These organs are frequently associated with chronic stress and injury during life, subjecting these tissues to frequent regeneration and to the risk of developing disease-associated cancers. The possibility of generating human 3D culture systems, named organoids, that resemble histologically and functionally specific organs, has opened up potential applications in the analysis of the cellular and molecular mechanisms involved in epithelial wound healing and regenerative therapy. Here, we review how during normal development homeostasis takes place, and the role of the microenvironmental niche cells in the intestinal stem cell crypt as an example. Then, we introduce the notion of a perturbed niche during disease conditions affecting the esophageal-stomach junction and the colon, and describe the potential applications of organoid models in the analysis of human gastrointestinal disease mechanisms. Finally, we highlight the perspectives of organoid-based regenerative therapy to improve the repair of the epithelial barrier.
胃肠道是一个从口腔到食管、胃、肠和肛门的连续器官系列，使消化得以发生。这些器官在一生中经常与慢性应激和损伤有关，使这些组织频繁再生，并面临发展与疾病相关的癌症的风险。生成类似于组织学和功能上特定器官的人类 3D 培养系统（称为类器官）的可能性，为分析涉及上皮创伤愈合和再生治疗的细胞和分子机制开辟了潜在的应用。在这里，我们回顾了正常发育过程中如何维持体内平衡，以及微环境龛细胞在肠干细胞隐窝中的作用，以肠道为例。然后，我们介绍了在影响食管-胃交界处和结肠的疾病条件下，龛位受到干扰的概念，并描述了类器官模型在分析人类胃肠道疾病机制中的潜在应用。最后，我们强调了基于类器官的再生疗法的观点，以改善上皮屏障的修复。
