Wellcome Trust-Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom.
Department of Genetics, University of Cambridge, Cambridge, United Kingdom.
Physiology (Bethesda). 2017 Jul;32(4):278-289. doi: 10.1152/physiol.00005.2017.
Among the endodermal tissues of adult mammals, the gastrointestinal (GI) epithelium exhibits the highest turnover rate. As the ingested food moves along the GI tract, gastric acid, digestive enzymes, and gut resident microbes aid digestion as well as nutrient and mineral absorption. Due to the harsh luminal environment, replenishment of new epithelial cells is essential to maintain organ structure and function during routine turnover and injury repair. Tissue-specific adult stem cells in the GI tract serve as a continuous source for this immense regenerative activity. Tissue homeostasis is achieved by a delicate balance between gain and loss of cells. In homeostasis, temporal tissue damage is rapidly restored by well-balanced tissue regeneration, whereas prolonged imbalance may result in diverse pathologies of homeostasis and injury repair. Starting with a summary of the current knowledge of GI tract homeostasis, we continue with providing models of acute injury and chronic diseases. Finally, we will discuss how primary organoid cultures allow new insights into the mechanisms of homeostasis, injury repair, and disease, and how this novel 3D culture system has the potential to translate into the clinic.
在成年哺乳动物的内胚层组织中，胃肠道（GI）上皮表现出最高的周转率。随着摄入的食物沿着胃肠道移动，胃酸、消化酶和肠道常驻微生物有助于消化以及营养和矿物质的吸收。由于腔内环境恶劣，在常规更新和损伤修复过程中，补充新的上皮细胞对于维持器官结构和功能至关重要。胃肠道中的组织特异性成体干细胞是这种巨大的再生活动的持续来源。组织稳态是通过细胞的获得和损失之间的微妙平衡来实现的。在稳态中，通过平衡良好的组织再生，迅速恢复暂时的组织损伤，而长时间的失衡可能导致稳态和损伤修复的多种病理。本文首先总结了目前对胃肠道稳态的认识，然后提供了急性损伤和慢性疾病的模型。最后，我们将讨论原代类器官培养如何为稳态、损伤修复和疾病的机制提供新的见解，以及这种新型的 3D 培养系统如何有可能转化为临床应用。
