The Francis Crick Institute, 1 Midland Road, London NW1 1AT, United Kingdom.
The Francis Crick Institute, 1 Midland Road, London NW1 1AT, United Kingdom.
Curr Opin Pharmacol. 2020 Feb;50:100-106. doi: 10.1016/j.coph.2020.02.001. Epub 2020 Mar 30.
Normal activity and functional integration of the enteric nervous system (ENS) into the gut tissue circuitry and the luminal ecosystem are essential for digestive physiology and human health. A range of debilitating gastrointestinal disorders are linked to ENS dysfunction, caused either by developmental deficits, such as congenital megacolon (Hirschsprung's disease-HSCR) or a host of acquired intestinal neuropathies with unclear molecular or cellular pathogenesis. Recent advances in cell engineering underscore the potential use of cell replacement technologies for the treatment of ENS disorders. This review will highlight strategies used to derive ENS lineages from various tissue sources intended for cell therapy and disease modelling. We will also describe how a developmental atlas of the mammalian ENS re-constructed from single cell genomics data is an essential reference for shaping future therapeutic approaches in regenerative enteric neuroscience and neuro-gastroenterology.
正常的肠神经系统（ENS）活动和功能与肠道组织回路和腔生态系统的整合，是消化生理学和人类健康的必要条件。一系列使人虚弱的胃肠道疾病与 ENS 功能障碍有关，这些功能障碍要么是由先天缺陷引起的，例如先天性巨结肠（先天性巨结肠 - HSCR），要么是由许多原因不明的分子或细胞发病机制引起的获得性肠神经病。细胞工程的最新进展强调了细胞替代技术在治疗 ENS 疾病方面的潜在用途。本综述将重点介绍从各种组织来源获得 ENS 谱系的策略，这些策略旨在用于细胞治疗和疾病建模。我们还将描述如何从单细胞基因组学数据重建哺乳动物 ENS 的发育图谱，这对于塑造再生肠神经科学和神经胃肠病学的未来治疗方法是必不可少的参考。
