School of Medicine, Western Sydney University, Campbelltown, NSW 2560, Australia.
Medical Sciences Research Group, Western Sydney University, Campbelltown, NSW 2560, Australia.
Int J Mol Sci. 2017 Sep 26;18(10):2059. doi: 10.3390/ijms18102059.
Effective digestion requires propagation of food along the entire length of the gastrointestinal tract. This process involves coordinated waves of peristalsis produced by enteric neural cell types, including different categories of interstitial cells of Cajal (ICC). Impaired food transport along the gastrointestinal tract, either too fast or too slow, causes a range of gut motility disorders that affect millions of people worldwide. Notably, loss of ICC has been shown to affect gut motility. Patients that suffer from gut motility disorders regularly experience diarrhoea and/or constipation, insomnia, anxiety, attention lapses, irritability, dizziness, and headaches that greatly affect both physical and mental health. Limited treatment options are available for these patients, due to the scarcity of human gut tissue for research and transplantation. Recent advances in stem cell technology suggest that large amounts of rudimentary, yet functional, human gut tissue can be generated in vitro for research applications. Intriguingly, these stem cell-derived gut organoids appear to contain functional ICC, although their frequency and functional properties are yet to be fully characterised. By reviewing methods of gut organoid generation, together with what is known of the molecular and functional characteristics of ICC, this article highlights short- and long-term goals that need to be overcome in order to develop ICC-based therapies for gut motility disorders.
有效的消化需要食物沿着整个胃肠道传播。这个过程涉及到由肠神经细胞类型产生的蠕动波的协调，包括不同类别的 Cajal 间质细胞（ICC）。胃肠道内食物运输的障碍，无论是过快还是过慢，都会导致一系列影响全球数百万人的肠道运动障碍。值得注意的是，ICC 的丧失已被证明会影响肠道运动。患有肠道运动障碍的患者经常经历腹泻和/或便秘、失眠、焦虑、注意力不集中、易怒、头晕和头痛，这极大地影响了身心健康。由于用于研究和移植的人类肠道组织稀缺，这些患者的治疗选择有限。干细胞技术的最新进展表明，可以在体外生成大量原始但功能齐全的人类肠道组织，用于研究应用。有趣的是，这些干细胞衍生的肠道类器官似乎含有功能性 ICC，尽管它们的频率和功能特性尚未完全描述。通过回顾肠道类器官生成的方法，以及 ICC 的分子和功能特征，本文强调了为开发用于肠道运动障碍的 ICC 为基础的治疗方法需要克服的短期和长期目标。
